Fused thiophone derivatives and drugs containing the same as the active ingredient

ABSTRACT

The present invention relates to a fused thiophene derivative of the formula (I) (wherein all the symbols are defined as described in the specification) and an inhibitor of producing interleukin-6 and/or interleukin-12 comprising the said derivative as an active ingredient.  
     A fused thiophene derivative of the formula (I) is useful as an agent for the prevention and/or treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi&#39;s sarcoma, rheumatoid arthritis, gammopathy, Castleman&#39;s disease, atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, infectious diseases.

TECHNICAL FIELD

[0001] The present invention relates to fused thiophene derivatives andinhibitors of producing Interleukin-6 (abbreviated as IL-6 hereafter)and/or Interleukin-12 (abbreviated as IL-12 hereafter) containing fusedthiophene derivatives as an active ingredient.

[0002] More particularly, the present invention relates to inhibitors ofproducing IL-6 and/or IL-12 comprising, as an active ingredient, fusedthiophene derivatives of the formula (I)

[0003] (wherein all the symbols are as defined hereafter.) and non-toxicsalts thereof, novel fused thiophene derivatives of the said formula(IA) or non-toxic salts thereof and methods for preparation thereof.

[0004] Moreover, the present invention relates to a method forpreparation of a compound of the formula (XI) which is an intermediatefor the compounds of the formula (I).

BACKGROUND

[0005] Cytokine is a multifunctional factor which plays an importantrole in the host defence system of living body and it relates to variouslife phenomena. However, there are many diseases which may be caused byoverproduction thereof or by overresponse thereto.

[0006] IL-6 is a cytokine produced from various cells, e.g. T cells, Bcells, macrophages, kidney mesangial cells, fibroblasts etc., and itsvarious physiological effects are known e.g. induction of B celldifferentiation to antibody-producing cells, activation of T cells,increase of platelets, and production of acute phase protein from livercells etc. But, an abnormal production of IL-6 has been observed invarious inflammations, autoimmune diseases and neoplastic diseases andit is suggested that IL-6 plays a certain role in the causes of suchpathophysiological situations. In the experiment using an animal modelin which IL-6 was forcibly expressed, various types of diseases could beobserved and such results strongly suggest the existence of relationshipbetween the abnormal production of IL-6 and the cause of certaindiseases (Biochem. J., 265, 621 (1990), Immunol. Today, 11, 443 (1990),J. Autoimmun., 5 Suppl A, 123 (1992), Clin. Immunol. Immunopathol., 62,S60 (1992)).

[0007] IL-12 is a cytokine produced from macrophages and dendritic cellsetc. and its effects are known; e.g. activation of natural killer(abbreviated as NK hereafter) cells, induction of Interferon-γ(abbreviated as IFN-γ hereafter) production from NK cells and T cells,and regulation of Th1 and Th2 balance etc. Helper T cells are classifiedinto Th1 which stimulates cellular-mediated immunity and Th2 whichassists humoral immunity. IL-12 functions to induce Th1 from helper Tcell precursors. It is thought that succeedingly, IL-12 inducesproduction of IFN-γ from Th1 cells (which are further differentiated)and accelerates killer activity, so that IL-12 plays a role as a maincytokine causing inflammatory immune reaction which leads to organdisorders (Blood, 84, 4008 (1994)).

[0008] Therefore, inhibition of IL-6 and/or IL-12 production(s) isexpected to improve various kinds of diseases such as inflammatorydiseases as a representative The present invention is targeted for thesecytokines and provides novel medicines through inhibiting the productionthereof.

[0009] Clinical application of the compounds of the present inventioninvolves those diseases which may be caused and be changed to worse byabnormal production of IL-6 and/or IL-12 or by overresponse to them.Inhibitors of producing IL-6 may be used for the prevention and/ortreatment of various inflammatory diseases, sepsis, multiple myeloma,plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis,renal cell carcinoma, Kaposi's sarcoma, rheumatoid arthritis,gammopathy, Castleman's disease, atrial myxoma, diabetes mellitus,autoimmune diseases (J. Immunol., 145, 4185 (1990), J. Exp. Med., 172:1505 (1990), J. Clin. Invest., 87,739 (1991), J. Clin. Invest., 89 1681(1992), EMBO J., 1, 1189 (1994), Hematol. Oncol. Clin. North Am., 11 159(1997)). Inhibitors of producing IL-12 may be used for the preventionand/or treatment of various inflammatory diseases, diabetes mellitus,hepatitis, multiple sclerosis, colitis, graft versus host immunediseases, rheumatoid arthritis, infectious diseases, autoimmune diseases(J. Exp. Med., 181, 817 (1995), J. Exp. Med., 181, 381 (1995), J. Exp.Med., 182 128, (1995), Ann, NY Acad. Sci., 795, 371 (1996), Int.Immunol., 8, 569 (1996), Proc. Natl. Acad. Sci. USA, 92, 4823 (1996)).

[0010] Further, a compound of the formula (Xl) is an importantintermediate of pharmaceutical agents and an efficient method forpreparation thereof has been desired.

[0011] For example,

[0012] (1) In the specifications of U.S. Pat. No. 3,629,438 and U.S.Pat. No. 3,686,216, it is disclosed that a benzothiophene-1,1-dioxidederivative of the formula (X)

[0013] (wherein X^(x) is halogen, nitro, alkyl, alkoxy, haloalkyl,carboxy or sulfonylhalide,

[0014] Y^(x) is hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy,

[0015] Z^(x) is alkyl, alkoxy, halogen, carboxy, haloalkyl or nitro,

[0016] aX is 0 or an integer of 2,

[0017] bX is an integer of 2,

[0018] cX is 0 or an integer of 1˜5 or

[0019] dX is 0 or an integer of 1˜4.)

[0020] has an anti-fungal and anti-vital activities.

[0021] (2) In the specification of FR1585930, a compound of the formula(Y)

[0022] (wherein R^(1Y) is hydrogen, halogen or C1˜3 alkyl; R^(2Y) andR^(3Y) are hydrogen or C1˜3 alkyl) is described as an intermediate ofdiuretic agent, but there is no description about its biologicalactivity.

[0023] (3) In the specification of SU591474, it is described that acompound of the formula (Z)

[0024] (wherein R^(Z), R^(1Z), R^(2Z) and R^(3Z) are hydrogen ormethyl.) has an anti-spasm activity.

[0025] (4) In the specification of EP50326, it is described that acompound of the formula (U)

[0026] (wherein R^(1U) and R^(2U) are each hydrogen or C1˜6 alkyl, C3˜6cycloalkyl or phenyl which may be substituted with 1-2 of halogen,hydroxy, C1˜6 alkyl or alkoxy, R^(3U) is hydrogen or Z^(U), Z^(U) isC1˜6 alkyl or CR^(4U)R^(5U)R^(6U), R^(4U) and R^(5U) are hydrogen orC1˜6 alkyl, R^(6U) is COOH, CH₂—OH, C1˜6 alkoxycarbonyl orhydroxyaminocarbonyl, X^(U) is hydrogen, halogen or C1˜6 alkyl, nU is 1or 2, mU is 0˜2) has a diuretic activity (In the explanation of groups,essential parts are extracted).

[0027] (5) In the specification of WO9527710, it is described that acompound of the formula (V)

[0028] (wherein R^(1V) is t-butyl, R^(1V) is hydrogen, lower alkyl oracyl, a broken line is arbitrary bond, R^(2V) and R^(3V) are hydrogen,alkyl which may be substituted or alkenyl which may be substituted,R^(4V) does not represent anything when arbitrary bond exists andrepresents the same meaning as R^(1V) when arbitrary bond does not existand nV is 0˜2.) has an activity as antioxidant of low-densitylipoprotein (LDL) (In the explanation of groups, essential parts areextracted).

[0029] (6) In the specification of Japanese Patent Application Kokai Hei10-298180, it is described that a compound of the formula (W)

[0030] (wherein Z^(W) is oxygen atom or sulfur atom; R^(1W), R^(2W),R^(3W) and R^(4W) are the same or different, are hydrogen etc.); E^(W)and F^(W) are the same or different, are nitrogen atom or CH which maybe substituted with X^(W) or Y^(W); X^(W) is straight or branched C1-6alkyloxy, C3-8 cycloalkyloxy or straight or branched C1-3 alkyloxysubstituted with C3˜8 cycloalkyl; Y is

[0031] (wherein G^(W) is —CONH—, O(O)O—, —NHCO— or —OC(O)—; R^(5W) is(a) straight or branched C1-6 alkyl, (b) C3-8 cycloalkyl, (c) C7-12spiroalkyl, (d) C7-12 bicycloalkyl, (e) aryl, (f) aralkyl, (g)heteroarylalkyl, (h) non-aromatic heterocyclic ring which may besubstituted with phenyl or (i) C3-8 cycloalkyl-C1˜3 alkyl. Each of themmay be substituted with one or more of substituent selected from a groupconsisting of i) straight or branched C1-6 alkyl, ii) straight orbranched C1-8 alkyloxy, iii) C1-3 haloalkyl, iv) halogen, v) C3-8cycloalkyl, vi) carboxy, vii) alkyloxycarbonyl, viii) acyl, ix) formyland x) nitro; nW is an integer of 1-3, pW is an integer of 1-3,(CH₂)_(w) and (CH₂)_(pW) may be substituted with a straight or branchedC1-6 alkyl or C1-3 haloalkyl) has an antagonistic activity againstdopamine receptor.

[0032] (7) In the specification of Japanese Patent Application Kokai Hei10-513470, it is described that a compound of the formula (T)

[0033] [wherein R^(1T) and R^(3T) are independently hydrogen, —CH₃,—C(O)—(C1˜6 alkyl), or —C(O)—Ar^(T) (Ar^(T) is phenyl which mayoptionally be substituted); R^(2T) is selected from a group consistingof pyrrolidino, hexamethyleneimino and piperidino], a pharmaceuticallyacceptable salt thereof or a solvent additive has an activity ofinhibiting the effect of IL-6.

[0034] (8) In the specification of Japanese Patent Application Kokai Hei11-49765, it is described that a compound of the formula (S)

[0035] [wherein each R^(1S) and R^(2S) is hydrogen or hydrocarbon groupwhich may contain substituent(s) or R^(1S) and R^(2S) taken togetherwith the neighboring carbon atom represents 3- to 8-membered homo orheterocyclic ring which may contain substituent(s), R^(3S) is hydrogenor lower alkyl which may contain subtstituent(s) or aromatic group whichmay contain substituent(s), R^(4S) is (1) aromatic group which maycontain substituent(s), (2) aliphatic hydrocarbon which containsaromatic group (this group is unsubstituted or substituted.) and whichmay contain additional substituent(s) or (3) acyl, X^(S) and Y^(S) areeach oxygen atom or sulfur atom which may be oxidized,

is single bond or double bond, ring A^(S) is benzene ring which containsa group of the formula —X^(S)R^(4S) (wherein each symbols represent thesame meaning as defined hereinbefore) and which may contain additionalsubstituent(s), with the proviso that when

is single bond and both XS and YS are oxygen atom, then R⁴⁵ is notacyl.] or a salt thereof have an excellent inhibitory effect ofneurodegeneration.

[0036] (9) Further, the following compounds are known.

[0037] Compound (1):3-(Thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene(Maybridge, Catalog No. KM 08156),

[0038] Compound (2):6-Nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene(Maybridge, catalog No. KM 08165),

[0039] Compound (3):3-(Thiophen-2-yl)thio-2,3-dihydro-11-dioxidebenzo[b]thiophene(Maybridge, Catalog No. KM 08138),

[0040] Compound (4):3-Phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge,Catalog No. KM 08140),

[0041] Compound (5): 4,5-Dimethyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 102036-04-4),

[0042] Compound (6): 4,6-Dimethyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 102036-05-5),

[0043] Compound (7): 4,7-Dimethyl-11-dioxidebenzo[b]thiophene (CASRegistry No. 102036-06-6),

[0044] Compound (8): 5,6-Dimethyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 102036-07-7),

[0045] Compound (9): 5,7-Dimethyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 102036-08-8),

[0046] Compound (10) 6,7-Dimethyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 102036-09-9),

[0047] Compound (11) 4-Carboxymethyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 102539-83-3),

[0048] Compound (12):6-(2,2-Bis(ethoxycarbonyl)ethenyl)amino-1,1-dioxidebenzo[b]thiophene(CAS Registry No. 118675-43-7),

[0049] Compound (13): 4-Methylaminocarbonyloxy-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 13687-26-8),

[0050] Compound (14):5-(2-(N-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino)ethyl)-1,1-dioxidebenzo[b]thiophene(CAS Registry No. 188110-86-3),

[0051] Compound (15): 5-(2-Hydroxyethyl)-1,1-dioxidebenzo[b]thiophene(CAS Registry No. 188111-49-1),

[0052] Compound (16): 5-Bromo-7-methyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 19076-24-5),

[0053] Compound (17): 7-Bromo-5-methyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 19076-25-6),

[0054] Compound (18): 5-Bromo-6-methyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 19076-26-7),

[0055] Compound (19): 5-Bromo-4-methyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 19076-27-8),

[0056] Compound (20): 6-Bromo-5-methyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 19076-28-9),

[0057] Compound (21): 4-Bromo-5-methyl-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 19076-29-0),

[0058] Compound (22): 6-Amino-1,1-dioxidebenzo[b]thiophene (CAS RegistryNo. 20503-40-6),

[0059] Compound (23): 6-Acetyamino-1,1-dioxidebenzo[b]thiophene (CASRegistry No. 20503-41-7),

[0060] Compound (24):6-(4-Diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene (CAS Registry No.33431-95-7),

[0061] Compound (25): 1,1-Dioxidethieno[2,3-b]pyridine (CAS Registry No.37049-39-1),

[0062] Compound (26): 1,1-Dioxidethieno[3,2-b]pyridine (CAS Registry No.37049-40-4),

[0063] Compound (27): 1,1-Dioxidethieno([2,3-c]pyridine (CAS RegistryNo. 37049-41-5),

[0064] Compound (28): 5-Amino-1,1-dioxidebenzo[b]thiophene (CAS RegistryNo. 51956-01-5),

[0065] Compound (29):5-(3-Methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene(GAS Registry No. 51956-06-0),

[0066] Compound (30):4-(2-(1,1-Dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene(CAS Registry No. 57011-92-4),

[0067] Compound (31): 7-Methyl-1,1-dioxidethieno[2,3-c]pyridine (CASRegistry No. 76905-90-3),

[0068] Compound (32): 1,1-Dioxidebenzo[b]thiophene (CAS Registry No.825-44-5),

[0069] Compound (33): 4-(4-Methoxyphenyl)-1,1-dioxidethieno[3,2-c]pyridine (CAS Registry No. 97104-25-1).

[0070] (10) In addition, as to a method for preparation of a compound ofthe formula (XI), for example, the method of the following ReactionScheme 2 is known.

[0071] These are described in detail in Nihonkagakuzasshi 1966, 87(2),186-189, J. Org. Chem., 1953, Vol. 18, 1511 and J. Org. Chem. 1973, Vol.38, 146.

[0072] In Reaction Scheme 2, Me is methyl, Ac is acetyl and NBS isN-bromosuccinimide.

[0073] The above method of Reaction Scheme 2 requires 5 or 6 steps intotal and Ag₂O, which is an expensive reagent, in oxidation reactionfrom the compound of the formula (XI-A-6) to the compound of the formula(XI).

[0074] Further, in the specification of Japanese Patent ApplicationKokai Hei 6-49058, the following Reaction Scheme 3 is disclosed as amethod for preparation of the compound of the formula (XI).

[0075] In Reaction Scheme 3, Et is ethyl.

[0076] The above method of Reaction Scheme 3 requires 5 steps in totaland the total yield is around 2˜3%.

[0077] In Tetrahedron Letters, 1996, Vol. 37, No. 19, 3243 andTetrahedron Letters 1990, Vol.31, No.28, 4011, a reaction wherein ketoneis converted into nitrile, followed by dehydrogenation to give aromaticring is disclosed (Reaction Scheme 4).

[0078] In Reaction Scheme 4, TMS is trimethylsilyl, DDQ is2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

[0079] This reaction is a method for preparation of aromatic nitrile ofthe formula (XI-C-2) which comprises that cyclic ketone of the formula(XI-C-1) is converted into cyanohydrin, followed by dehydration to givenitrile of the formula (XI-C-2), and then followed by dehydrogenation byan oxidizer.

DISCLOSURE OF THE INVENTION

[0080] The present inventors have investigated to find new compoundspossessing an inhibitory activity of producing IL-6 and/or IL-12, sothat the present inventors have found that the purpose has been achievedby fused thiophene derivatives of the formula (I).

[0081] Fused heterocyclic compounds of the formula (I) of the presentinvention has not been known as inhibitors of producing IL-6 and/orIL-12 at all. Further, a fused thiophene derivative of the formula (IA)is a novel compound which is not known at all.

[0082] In addition, the present inventors have investigated to find anefficient method for preparation at a low cost, so that the presentinventor have found a method of the following Reaction Scheme 5.

[0083] The old methods require 5-6 steps, whereas the method of thepresent invention diminishes to 3 steps in total, so it become possibleto produce efficiently. In addition, it is also confirmed that inmass-production of it, the cost for the production is reduced, so thatthe present inventors have completed the present invention.

[0084] The present invention relates to

[0085] (1) an inhibitor of producing Interleukin-6 and/or Interleukin-12comprising, as an active ingredient, a fused thiophene derivative of theformula (I)

[0086] [wherein

is a single or double bond, Y is (i)

[0087] or

[0088] (ii) hydrogen

[0089] (with a proviso that when

is a double bond, Y is hydrogen, and when

is a single bond, Y is

[0090] m and n are each independently 0 or an integer of 1-2,

[0091] p is 0 or an integer of 1-4,

[0092] q is 0 or an integer of 1-5,

[0093] Z is single bond, C1-8 alkylene, C2-8 alkenylene or C2-8alkynylene,

[0094] is

[0095] (i) benzene ring or

[0096] (ii) 6-membered monocyclic hetero aryl containing 1-2 nitrogenatom(s),

[0097] is

[0098] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0099] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, each R¹of (R¹)p is independently,

[0100] (i) C1-8 alkyl,

[0101] (ii) C2-8 alkenyl,

[0102] (iii) C2-8 alkynyl,

[0103] (iv) nitro,

[0104] (v) cyano,

[0105] (vi) halogen,

[0106] (vii) Cyc¹,

[0107] (viii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted withhalogen or Cyc¹or

[0108] (ix) —A¹—A²—A³,

[0109] A¹ is

[0110] (i) single bond,

[0111] (ii) C1-8 alkylene,

[0112] (iii) C2-8 alkenylene or

[0113] (iv) C2-8 alkynylene,

[0114] A² is

[0115] (i) —O—,

[0116] (ii) —NR³—

[0117] (iii) —C(O)—,

[0118] (iv) —CH(OH)—,

[0119] (v) —C(O)NR⁴—,

[0120] (vi) —NR¹¹C(O)—,

[0121] (vii) —C(O)O—,

[0122] (viii) —OC(O)—,

[0123] (ix) —SO₂NR⁶—,

[0124] (x) —NR⁷SO₂—,

[0125] (xi) —C(O)NR⁹O—,

[0126] (xii) —OC(O)NR¹⁰—,

[0127] (xiii) —NR¹¹C(O)NR¹²—,

[0128] (xiv) —NR¹³C(O)O— or

[0129] (xv) —OC(O)O—

[0130] (wherein R³, R⁴, R⁵, R⁶ R⁷, R⁹, R¹⁰, R¹¹, R¹² and R¹³ are eachindependently, hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substitutedwith Cyc¹, —OR¹⁴ (wherein R¹⁴ is hydrogen or C1-8 alkyl.) or cyano, withthe proviso that the linkage of the right side of each group representedby A² binds to A³.

[0131] A³ is

[0132] (i) hydrogen,

[0133] (ii) C1-8 alkyl,

[0134] (iii) C2-8 alkenyl,

[0135] (iv) C2-8 alkynyl,

[0136] (v) Cyc¹ or

[0137] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with1-3 groups selected from the following (a)-(i):

[0138] (a) halogen,

[0139] (b) cyano,

[0140] (c) —P(O)(R¹⁵)₂,

[0141] (d) —Si(R¹⁶)₃,

[0142] (e) Cyc¹,

[0143] (f) —C(O)R¹⁷,

[0144] (g) —OR¹⁸,

[0145] (h) —NR¹⁹R²⁰,

[0146] (i) —SR²¹;

[0147] plural R¹⁵s are each independently, hydroxy or C1-8 alkoxy,

[0148] plural R¹⁶s are each independently C1-8 alkyl,

[0149] R¹⁷ is

[0150] (i) hydrogen,

[0151] (ii) C1-8 alkyl,

[0152] (iii) hydroxy,

[0153] (iv) C1-8 alkoxy,

[0154] (v) Cyc¹ or

[0155] (vi) —NR²²R²³ (wherein R²² is hydrogen, C1-8 alkyl, phenyl orC1-8 alkyl substituted with phenyl, R²³ is hydrogen, C1-8 alkyl, Cyc¹ orC1-8 alkyl substituted with Cyc¹ or NR²⁴R²⁵ (R²⁴ and R²⁵ are eachindependently hydrogen, C1-8 alkyl, phenyl, C1-8 alkyl substituted withphenyl.).),

[0156] R¹⁸ is

[0157] (i) hydrogen,

[0158] (ii) C1 -8 alkyl,

[0159] (iii) C2-8 alkenyl,

[0160] (iv) Cyc¹ or

[0161] (v) C1-8 alkyl substituted with Cyc′, Si(R²⁶)₃ (wherein pluralR²⁷ are each independently C1-8 alkyl.) or —OR²⁷ (wherein R²⁷ ishydrogen, C1-8 alkyl or C2-5 acyl.),

[0162] R¹⁹ is

[0163] (i) hydrogen,

[0164] (ii) C1-8 alkyl,

[0165] (iii) phenyl or

[0166] (iv) C1-8 alkyl substituted with phenyl,

[0167] R²⁰ is

[0168] (i) hydrogen,

[0169] (ii) C1-8 alkyl or

[0170] (iii) —C(O)R²⁸ (wherein R²⁸ is C1-8 alkyl, C1-8 alkoxy, Cyc¹ orNR²⁹R³⁰ (wherein R²⁹ and R³⁰ are each independently, hydrogen or C1-8alkyl.).),

[0171] (iv) Cyc¹ or

[0172] (v) C1-8 alkyl substituted with Cyc¹ or cyano,

[0173] R²¹ is

[0174] (i) hydrogen,

[0175] (ii) C1-8 alkyl or

[0176] (iii) Cyc¹,

[0177] Cyc¹ is

[0178] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0179] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, thesaid carbocyclic ring or heterocyclic ring may be substituted with oneor more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv)oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy,(ix) halogen, (x) diphenylmethyl, (xi) triphenylmethyl, (xii) Cyc²,(xiii) —OR³, (xiv) —SR³², (xv) —NR³³R³⁴, (xvi) —SO₂NR³⁵ R³⁶ (xvii)—C(O)R³⁷ or (xviii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substitutedwith Cyc², hydroxy, halogen or —C(O)—Cyc²,

[0180] R³¹ and R³² are each independently, hydrogen, C1-8 alkyl or Cyc²,

[0181] R³³ is hydrogen or C1-8 alkyl,

[0182] R³⁴ is hydrogen, C1-8 alkyl or —C(O)-Cyc²,

[0183] R³⁷ is hydrogen or C1-8 alkyl, R³⁶ is hydrogen, C1-8 alkyl orCyc²,

[0184] R³⁷ is hydrogen, C1-8 alkyl, —OR³⁸, —NR³⁹R⁴⁰, Cyc², or C1-8 alkylsubstituted with Cyc² or —C(O)-Cyc²,

[0185] R³⁸, R³⁹ and R⁴⁰ are each independently, hydrogen, C1-8 alkyl, orC1-8 alkyl substituted with Cyc²,

[0186] Cyc² is

[0187] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0188] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0189] the said carbocyclic ring or heterocyclic ring may be substitutedwith one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii)trihalomethoxy, (ix) halogen, (x) —OR⁴¹, (xi) —SR⁴², (xii) —NR⁴³R⁴⁴,(xiii) —SO₂NR⁴⁵R⁴⁶, (xiv) —C(O)R⁴⁷, (xv) C1-8 alkyl, C2-8 alkenyl orC2-8 alkynyl substituted with hydroxy or halogen or (xvi) phenyl,

[0190] R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵ and R⁴⁶ are each independently, hydrogenor C1-8 alkyl,

[0191] R⁴⁷ is hydrogen, C1-8 alkyl or C1-8 alkoxy

[0192] each R² of (R²)q is independently,

[0193] (i) C1-8 alkyl,

[0194] (ii) C2-8 alkenyl,

[0195] (iii) C2-8 alkynyl,

[0196] (iv) —OR⁴⁸

[0197] (v) —NR⁴⁹R⁵⁰,

[0198] (vi) —C(O)R⁵¹,

[0199] (vii) nitro,

[0200] (viii) cyano,

[0201] (ix) halogen or

[0202] (x) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with—OR⁴⁸, —NR⁴⁹R⁵⁰, —C(O)R⁵¹, halogen or Cyc³,

[0203] R⁴⁸ is

[0204] (i) hydrogen,

[0205] (ii) C1-8 alkyl,

[0206] (iii) C2-8 alkenyl,

[0207] (iv) C2-8 alkynyl,

[0208] (v) Cyc³ or

[0209] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted withhalogen, —OR⁵², —NR⁵³R⁵⁴, —C(O)R⁵⁵ or Cyc³,

[0210] R⁴⁹ and R⁵⁰ are each independently, hydrogen, C1-8 alkyl or—COR⁵⁹,

[0211] R⁵¹ is hydrogen, C1-8 alkyl, hydroxy, C1-8 alkoxy or —NR⁵⁰R⁶¹,

[0212] R⁵² is hydrogen, C1-8 alkyl, Cyc³, or C1-8 alkyl substituted withCyc³,

[0213] —R⁵³ and R⁵⁴ are each independently, hydrogen, C1-8 alkyl, C2-8alkenyl, C2-8 alkynyl or —C(O)R⁵⁶ (wherein R⁵⁶ is C1-8 alkyl, C1-8alkoxy, Cyc³, or C1-8 alkyl substituted with Cyc³),

[0214] R⁵⁵ is hydroxy, C1-8 alkoxy, or —NR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵⁸ areeach independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted withCyc³),

[0215] R⁵⁹ is C1-8 alkyl or C1-8 alkoxy,

[0216] R⁶⁰ and R⁶¹ are each independently, hydrogen or C1-8 alkyl,

[0217] Cyc³ is

[0218] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0219] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0220] the said carbocyclic ring or heterocyclic ring may be substitutedwith one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv)halogen, (v) cyano, (vi) hydroxy, (vii) benzyloxy, (viii) —NR⁶²R⁶³, (ix)—COOR⁶⁴, (x) trihalomethyl, (xi) trihalomethoxy, (xii) phenyl, (xiii)phenoxy, (xiv) phenylthio, (xv) C1-8 alkyl or C1-8 alkoxy substitutedwith phenyl, phenoxy, phenylthio, hydroxy, —NR⁶²R⁶³ or —COOR⁶⁴,

[0221] R⁶² and R⁶³ are each independently, hydrogen or C1-8 alkyl,

[0222] R⁶⁴ is hydrogen or C1-8 alkyl,

[0223] with the proviso that when A² is (vi) —NR⁵C(O)—, (x) —NR⁷SO₂—,(xiv) —NR¹³C(O)O— or (xv) —OC(O)O—, then A³ is not hydrogen.],

[0224] an N-oxide derivative thereof or a non-toxic salt thereof,

[0225] (2) a fused thiophene derivative of the formula (IA)

[0226] [wherein

is a single or double bond,

[0227] Y is (i)

[0228] or

[0229] (ii) hydrogen

[0230] (with a proviso that when

is a double bond, Y is hydrogen, and when

is a single bond, Y is

[0231] m and n are each independently 0 or an integer of 1-2,

[0232] p is 0 or an integer of 1-4,

[0233] q is 0 or an integer of 1-5,

[0234] Z is single bond, C1-8 alkylene, C2-8 alkenylene or C2-8alkynylene,

[0235] is

[0236] (i) benzene ring or

[0237] (ii) 6-membered monocyclic hetero aryl containing 1-2 nitrogenatom(s),

[0238] is

[0239] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0240] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0241] each R¹ of (R¹)p is independently,

[0242] (i) C1-8 alkyl,

[0243] (ii) C2-8 alkenyl,

[0244] (iii) C2-8 alkynyl,

[0245] (iv) nitro,

[0246] (v) cyano,

[0247] (vi) halogen,

[0248] (vii) Cyc¹,

[0249] (viii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted withhalogen or Cyc¹ or

[0250] (ix) —A¹—A²—A³,

[0251] A¹ is

[0252] (i) single bond,

[0253] (ii) C1-8 alkylene,

[0254] (iii) C2-8 alkenylene or

[0255] (iv) C2-8 alkynylene,

[0256] A ² is

[0257] (i) —O—,

[0258] (ii) —NR³—

[0259] (iii) —C(O)—,

[0260] (iv) —CH(OH)—,

[0261] (v) —C(O)NR⁴—,

[0262] (vi) —NR⁵C(O)—,

[0263] (vii) —C(O)O—,

[0264] (viii) —OC(O)—,

[0265] (ix) —SO₂NR⁶,

[0266] (x) —NR⁷SO₂—,

[0267] (xi) —C(O)NR⁹O—,

[0268] (xii) —OC(O)NR¹⁰—,

[0269] (xiii) —NR¹¹C(O)NR¹²—,

[0270] (xiv) —NR¹³C(O)O— or

[0271] (xv) —OC(O)O—

[0272] (wherein R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹² and R¹³ are eachindependently, hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substitutedwith Cyc¹, —OR¹⁴ (wherein R¹⁴ is hydrogen or C1-8 alkyl.) or cyano, withthe proviso that the linkage of the right side of each group representedby A² binds to A³.

[0273] A³ is

[0274] (i) hydrogen,

[0275] (ii) C1-8 alkyl,

[0276] (iii) C2-8 alkenyl,

[0277] (iv) C2-8 alkynyl,

[0278] (v) Cyc¹ or

[0279] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with1-3 groups selected from the following (a)-(i):

[0280] (a) halogen,

[0281] (b) cyano,

[0282] (c) —P(O)(R¹⁵)₂,

[0283] (d) —Si(R¹⁶)₃,

[0284] (e) Cyc¹,

[0285] (f) —C(O)R¹⁷,

[0286] (g) —OR¹⁸,

[0287] (h) —NR¹⁹R²⁰,

[0288] (i) —SR²¹;

[0289] plural R¹⁵s are each independently, hydroxy or C1-8 alkoxy,

[0290] plural R¹⁶s are each independently C1-8 alkyl,

[0291] R¹⁷ is

[0292] (i) hydrogen,

[0293] (ii) C1-8 alkyl,

[0294] (iii) hydroxy,

[0295] (iv) C1-8 alkoxy,

[0296] (v) Cyc¹ or

[0297] (vi) —NR²²R²³ (wherein R²² is hydrogen, C1-8 alkyl, phenyl orC1-8 alkyl substituted with phenyl, R²³ is hydrogen, C1-8 alkyl, Cyc¹ orC1-8 alkyl substituted with Cyc¹ or NR²⁴R²⁵ (R²⁴ and R²⁵ are eachindependently hydrogen, C1-8 alkyl, phenyl, C1-8 alkyl substituted withphenyl.).),

[0298] R¹⁸ is

[0299] (i) hydrogen,

[0300] (ii) C1-8 alkyl,

[0301] (iii) C2-8 alkenyl,

[0302] (iv) Cyc¹ or

[0303] (v) C1-8 alkyl substituted with Cyc¹, Si(R²⁶)₃ (wherein pluralR²⁶s are each independently C1-8 alkyl.) or —OR²⁷ (wherein R²⁷ ishydrogen, C1-8 alkyl or C2-5 acyl.),

[0304] R¹⁹ is

[0305] (i) hydrogen,

[0306] (ii) C1-8 alkyl,

[0307] (iii) phenyl or

[0308] (iv) C1-8 alkyl substituted with phenyl,

[0309] R²⁰ is

[0310] (i) hydrogen,

[0311] (ii) C1-8 alkyl or

[0312] (iii) —C(O)R²⁸ (wherein R²⁸ is C1-8 alkyl, C1-8 alkoxy, Cyc¹ orNR²⁹R³⁰ (wherein R²⁹ and R³⁰ are each independently, hydrogen or C1-8alkyl.).),

[0313] (iv) Cyc¹ or

[0314] (v) C1-8 alkyl substituted with Cyc¹ or cyano,

[0315] R²¹ is

[0316] (i) hydrogen,

[0317] (ii) C1-8 alkyl or

[0318] (iii) Cyc¹,

[0319] Cyc¹ is

[0320] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0321] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0322] the said carbocyclic ring or heterocyclic ring may be substitutedwith one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii)trihalomethoxy, (ix) halogen, (x) diphenylmethyl, (xi) triphenylmethyl,(xii) Cyc², (xiii) —OR³¹, (xiv) —SR², (xv) —NR³³R³⁴, (xvi) —SO₂NR³⁵R³⁶,(xvii) —C(O)R³⁷ or (xviii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynylsubstituted with Cyc², hydroxy, halogen or —C(O)-Cyc²,

[0323] R³¹ and R³² are each independently, hydrogen, C1-8 alkyl or Cyc²,

[0324] R³³ is hydrogen or C1-8 alkyl,

[0325] R³⁴ is hydrogen, C1-8 alkyl or —C(O)-Cyc²,

[0326] R³⁶ is hydrogen or C1-8 alkyl,

[0327] R³⁶ is hydrogen, C1-8 alkyl or Cyc²,

[0328] R³⁷ is hydrogen, C1-8 alkyl, —OR³⁸, —NR³⁹R⁴⁰, Cyc², or C1-8 alkylsubstituted with Cyc² or —C(O)—Cyc²,

[0329] R³⁶, R³⁹ and R⁴⁰ are each independently, hydrogen, C1-8 alkyl, orC1-8 alkyl substituted with Cyc²,

[0330] Cyc² is

[0331] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0332] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0333] the said carbocyclic ring or heterocyclic ring may be substitutedwith one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii)trihalomethoxy, (ix) halogen, (x) —OR⁴¹, (xi) —SR⁴², (xii) —NR⁴³R⁴⁴,(xiii) —SO₂NR⁴⁵R⁴⁶, (xiv) —C(O)R⁴⁷, (xv) C1-8 alkyl, C2-8 alkenyl orC2-8 alkynyl substituted with hydroxy or halogen or (xvi) phenyl,

[0334] R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵ and R⁴⁶ are each independently, hydrogenor C1-8 alkyl, R⁴⁷ is hydrogen, C1-8 alkyl or C1-8 alkoxy

[0335] each R² of (R²q is independently,

[0336] (i) C1-8 alkyl,

[0337] (ii) C2-8 alkenyl,

[0338] (iii) C2-8 alkynyl,

[0339] (iv) —OR⁴⁸,

[0340] (v) —NR⁴⁹R⁵⁰,

[0341] (vi) —C(O)R⁵¹,

[0342] (vii) nitro,

[0343] (viii) cyano,

[0344] (ix) halogen or

[0345] (x) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with—OR⁴⁸, -NR⁴⁹R⁵⁰, —C(O)R⁵¹, halogen or Cyc³,

[0346] R⁴⁸ is

[0347] (i) hydrogen,

[0348] (ii) C1-8 alkyl,

[0349] (iii) C2-8 alkenyl,

[0350] (iv) C2-8 alkynyl,

[0351] (v) Cyc³ or

[0352] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted withhalogen, —OR⁵², —

[0353] NR⁵³R⁵⁴, —C(O)R⁵⁵ or Cyc³,

[0354] R⁴⁹ and R⁵¹ are each independently, hydrogen, C1-8 alkyl or—COR⁵⁹,

[0355] R⁵¹ is hydrogen, C1-8 alkyl, hydroxy, C1-8 alkoxy or —NR⁶“R⁶,

[0356] R⁵² is hydrogen, C1-8 alkyl, Cyc³, or C1-8 alkyl substituted withCyc³,

[0357] R⁵³ and R⁵⁴ are each independently, hydrogen, C1-8 alkyl, C2-8alkenyl, C2-8 alkynyl or —C(O)R⁵⁶ (wherein R⁵⁶ is C1-8 alkyl, C1-8alkoxy, Cyc³, or C1-8 alkyl substituted with Cyc³),

[0358] R⁵⁵ is hydroxy, C1-8 alkoxy, or —NR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵⁸ areeach independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted withCyc³),

[0359] R⁵⁹ is C1-8 alkyl or C1-8 alkoxy,

[0360] R⁶⁰ and R⁶¹ are each independently, hydrogen or C1-8 alkyl,

[0361] Cyc³ is

[0362] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0363] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0364] the said carbocyclic ring or heterocyclic ring may be substitutedwith one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv)halogen, (v) cyano, (vi) hydroxy, (vii) benzyloxy, (viii) —NR⁶²R⁶³, (ix)—COOR⁶⁴, (x) trihalomethyl, (xi) trihalomethoxy, (xii) phenyl, (xiii)phenoxy, (xiv) phenylthio, (xv) C1-8 alkyl or C1-8 alkoxy substitutedwith phenyl, phenoxy, phenylthio, hydroxy, —NR⁶²R⁶³ or —COOR⁶⁴,

[0365] R⁶² and R⁶³ are each independently, hydrogen or C1-8 alkyl,

[0366] R⁶⁴ is hydrogen or C1-8 alkyl,

[0367] with the proviso that when

[0368] (1) when A² is (vi) —NR⁵C(O)—, (x) —NR⁷SO₂—, (xiv) —NR¹³C(O)O— or(xv) —OC(O)O—,

[0369] then A³ is not hydrogen,

[0370] (2) when

is a double bond and Y is hydrogen, then n is 1 or 2,

[0371] (3) when

is a single bond, Y is

[0372] n is 2,

[0373] m is 0 or 2, p is O or an integer of 1-4, ring A and ring B arebenzene ring, R¹ is C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro orC1-8 alkyl substituted with halogen, then q is not 0,

[0374] (4) when

is a single bond, Y is

[0375] n is 2,

[0376] m is 0 or 2, p is 0 or an integer of 1-4, ring A and ring B arebenzene ring, R¹ is C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro orC1-8 alkyl substituted with halogen, and q is an integer of 1-5, then R²is not C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro or C1-8 alkylsubstituted with halogen,

[0377] (5) when

is a double bond, Y is hydrogen, n is 2, p is 1 and ring A is benzenering, then R¹ is not halogen, C1-8 alkyl, phenylsulfonylamino,2-methylphenylsulfonylamino, 3-methylphenylsulfonylamino,4-methylphenylsulfonylamino, hydroxy, C1-8 alkoxy, nitro, or C1-8 alkoxysubstituted with carboxy, hydroxy, C1-8 alkoxycarbonyl orhydroxyaminocarbonyl,

[0378] (6) when

is a double bond, Y is hydrogen, n is 2, p is 2 and ring A is benzenering and one R¹ is phenylsulfonylamino, 2-methylphenyisulfonylamino,3-methylphenylsulfonylamino or 4-methylphenylsulfonylamino, then theother R¹ is not C1-8 alkyl,

[0379] (7) when

is a double bond, Y is hydrogen, n is 2, p is 2-3, ring A is benzenering, one R¹ is hydroxy, C1-8 alkoxy, or C1-8 alkoxy substituted withcarboxy, hydroxy, C1-8 alkoxycarbonyl or hydroxyaminocarbonyl, then theother R¹ is neither halogen nor C1-8 alkyl,

[0380] (8) when

is a double bond, Y is hydrogen, n is 2, p is 3-4 and ring A is benzenering, then two or three R¹ are not t-butyl at the same time, and

[0381] (9) the following compounds (1)-(32) are excluded:

[0382] (1)3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,

[0383] (2)6-nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,

[0384] (3)3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[blthiophene,

[0385] (4) 4,5-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0386] (5) 4,6-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0387] (6) 4,7-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0388] (7) 5,6-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0389] (8) 5,7-dimethyl-1,1-dioxidebenzo[b[thiophene,

[0390] (9) 6,7-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0391] (10) 4-carboxymethyl-1,1-dioxidebenzo[b]thiophene,

[0392] (11)6-(2,2-bis(ethoxycarbonyl)ethenyl)amino-1,1-ioxidebenzo[b]thiophene,

[0393] (12) 4-methylaminocarbonyloxy-1,1-dioxidebenzo[b]thiophene,

[0394] (13)5-(2-(N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino)ethyl)-1,1-dioxidebenzo[b]thiophene,

[0395] (14) 5-(2-hydroxyethyl)-1,1-dioxidebenzo[b]thiophene,

[0396] (15) 5-bromo-7-methyl-1,1-dioxidebenzo[b]thiophene,

[0397] (16) 7-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene,

[0398] (17) 5-bromo-6-methyl-1,1-dioxidebenzo[b]thiophene,

[0399] (18) 5-bromo-4-methyl-1,1-dioxidebenzo[b]thiophene,

[0400] (19) 6-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene,

[0401] (20) 4-bromo-5-methyl-1, -dioxidebenzo[b]thiophene,

[0402] (21) 6-amino-1,1-dioxidebenzo[b]thiophene,

[0403] (22) 6-acetylamino-1,1-dioxidebenzo[b]thiophene,

[0404] (23) 6-(4-diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene,

[0405] (24) 1,1-dioxidethieno[2,3-b]pyridine,

[0406] (25) 1,1 -dioxidethieno[3,2-b]pyridine,

[0407] (26) 1,1-dioxidethieno[2,3-c]pyridine,

[0408] (27) 5-amino-1,1-dioxidebenzo[b]thiophene,

[0409] (28)5-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene,

[0410] (29)4-(2-(1,1-dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene,

[0411] (30) 7-methyl-1,1-dioxidethieno[2,3-c]pyridine,

[0412] (31) 1,1-dioxidebenzo[b]thiophene or

[0413] (32) 4-(4-methoxyphenyl)-1,1-dioxidethieno[3,2-c]pyridine.],

[0414] an N-oxide derivative thereof or a non-toxic salt thereof,

[0415] (3) a method for preparation of a fused thiophene derivative ofthe formula (IA), an N-oxide derivative thereof or a non-toxic saltthereof and

[0416] (4) a method for preparation of a compound of the formula (XI)

[0417] which is characterized by cyanization of a compound of theformula (XII)

[0418] to obtain a compound of the formula (XIII)

[0419] then by subjecting to dehydration of the said compound of theformula (XII) to obtain a compound of the formula (XIV)

[0420] and then by subjecting to hydrolysis of the said compound of theformula (XIV).

DETAILED EXPLANATION OF THE INVENTION

[0421] Unless otherwise specified, all isomers are included in thepresent invention. For example, alkyl, alkenyl, alkynyl, alkoxy,alkylthio, alkylene, alkenylene and alkynylene group include straight orbranched ones. In addition, isomers on double bond, ring, fused ring(E—, Z—, cis-, trans-isomer), isomers generated from asymmetric carbonatom(s) (R—, S—, α—, β-isomer, enantiomer, diastereomer), opticallyactive isomers (D—, L—, d-, I-isomer), polar compounds generated bychromatographic separation (more polar compound, less polar compound),equilibrium compounds, mixtures thereof at voluntary ratios and racemicmixtures are also included in the present invention.

[0422] In the present invention, an N-oxide derivative of a compound ofthe formula (I) and (IA) means a compound wherein nitrogen atom(s) in acompound containing nitrogen atom(s) of the formula (I) and (IA) is(are) oxidized.

[0423] In the present invention, C1-8 alkyl means methyl, ethyl, propyl,butyl, pentyl, hexyl, heptyl, octyl and the isomers thereof.

[0424] C2-8 alkenyl means vinyl, propenyl, butenyl, pentenyl, hexenyl,heptenyl, octenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl,octadienyl, hexatrienyl, heptatrienyl, octatrienyl and the isomersthereof.

[0425] C2-8 alkynyl means ethynyl, propynyl, butynyl, pentynyl, hexynyl,heptynyl, octynyl and the isomers thereof.

[0426] C1-8 alkylene means methylene, ethylene, trimethylene,tetramethylene, pentamethylene, hexamethylene, heptamethylene,octamethylene and the isomers thereof.

[0427] C2-8 alkenylene means ethenylene, propenylene, butenylene,pentenylene, hexenylene, heptenylene, octenylene and the isomersthereof.

[0428] C2-8 alkynylene means ethynylene, propynylene, butynylene,pentynylene, hexynylene, heptynylene, octynylene and the isomersthereof.

[0429] Halogen means chloride, bromide, fluoride and iodide.

[0430] C1-8 alkoxy means methoxy, ethoxy, propoxy, butoxy, pentyloxy,hexyloxy, heptyloxy, octyloxy and the isomers thereof.

[0431] Trihalomethyl means methyl substituted with three atoms selectedfrom group consisting of chloride, bromide, fluoride and iodide atom.

[0432] Trihalomethoxyl means methoxyl substituted with three atomsselected from group consisting of chloride, bromide, fluoride and iodideatom.

[0433] C2-5 acyl means acetyl, propionyl, butyryl, valeryl and isomersthereof.

[0434] 6Membered monocyclic hetero aryl containing 1-2 nitrogen atom(s)includes, for example, pyridine, pyridine-N-oxide, pyrazine,pyrazine-N-monoxide, pyrazine-N-dioxide, pyrimizine,pyrimizine-N-monoxide, pyrimizine-N-dioxide, pyridazine,pyridazine-N-monoxide, pyridazine-N-dioxide ring etc.

[0435] C3-15 Mono-, bi- or tricyclic carbo ring includes, for example,cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane,cyclopenten, cyclohexen, cyclopentadien, cyclohexadien, benzene,penthalene, indene, naphthalene, azulene, florene, phenanthrene,anthracene, acenaphthylene, biphenylene, perhydropentalene,perhydroindene, dihydronaphthalene, tetrahydronaphthalene,perhydronaphthalene, perhydroazulene, perhydrofluorene,perhydrophenanthrene, perhydroanthracene, perhydroacenaphthylene,perhydrobiphenylene ring etc.

[0436] 4-18 Membered mono-, bi- or tricyclic hetero ring containing 1-4nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom includes4-18 membered mono-, bi- or tricyclic hetero aryl containing 1-4nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom orcorresponding hetero ring in which ring is saturated partially or fully.

[0437] The said 4-18 membered mono-, bi- or tricyclic hetero arylcontaining 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfuratom includes, for example, pyrrole, pyrrole-N-oxide, imidazole,triazole, tetrazole, pyrazole, pyridine, pyridine-N-oxide, pyrazine,pyrazine-N-monoxide, pyrazine-N-dioxide, pyrimizine,pyrimizine-N-monoxide, pyrimizine-N-dioxide, pyridazine,pyridazine-N-monoxide, pyridazine-N-dioxide, azepine, diazepine, furan,pyran, oxepine, oxazepine, thiophene, thiain (thiopyran), thiepine,oxazole, isoxazole, thiazole, isothiazole, oxadiazole, oxazine,oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine, thiadiazine,thiazepine, thiadiazepine, indole, isoindole, benzofuran, isobenzofuran,benzothiophene, isobenzothiophene, indazole, quinoline,quinoline-N-oxide, isoquinoline, isoquinoline-N-oxide, phthalazine,naphthyridine, naphthyridine-N-monoxide, naphthyridine-N-dioxide,quinoxaline, quinoxaline-N-monoxide, quinoxaline-N-dioxide, quinazoline,quinazoline-N-monoxide, quinazoline-N-dioxide, cinnoline, benzoxazole,benzothiazole, benzoimidazole, carbazole, acridine ring etc.

[0438] The said 4-18 membered mono-, bi- or tricyclic hetero ringcontaining 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfuratom in which ring is saturated partially or fully includes, forexample, pyrroline, pyrrolidine, pyrrolidine-N-oxide, imidazoline,imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine,dihydropyridine, dihydropyridine-N-oxide, dihydropyrazine,dihydropyrazine-N-monoxide, dihydropyrazine-N-dioxide,dihydropyrimizine, dihydropyrimizine-N-monoxide,dihydropyrimizine-N-dioxide, dihydropyridazine,dihydropyridazine-N-monoxide, dihydropyridazine-N-dioxide, piperidine,piperidine-N-oxide, piperazine, piperazine-N-monoxide,piperazine-N-dioxide, tetrahydropyrimizine,tetrahydropyrimizine-N-monoxide, tetrahydropyrimizine-N-dioxide,tetrahydropyridazine, tetrahydropyridazine-N-monoxide,tetrahydropyridazine-N-dioxide, dihydrofuran, tetrahydrofuran,dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene,dihydrothiain (dihydrothiopyran), tetrahydrothiain(tetrahydrothiopyran), dihydroxazole, tetrahydroxazole,dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole,tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole,morpholine, morpholine-N-oxide, thiomorpholine, thiomorpholine-N-oxide,indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran,dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene,perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, dihydroquinoline-N-oxide, tetrahydroquinoline,tetrahydroquinoline-N-oxide, perhydroquinoline,perhydroquinoline-N-oxide, dihydroisoquinoline,dihydroisoquinoline-N-oxide, tetrahydroisoquinoline,tetrahydroisoquinoline-N-oxide, perhydroisoquinoline,perhydroisoquinoline-N-oxide, dihydrophthalazine, tetrahydrophthalazine,perhydrophthalazine, dihydronaphthyridine,dihydronaphthyridine-N-monoxide, dihydronaphthyridine-N-dioxide,tetrahydronaphthyridine, tetrahydronaphthyridine-N-monoxi de,tetrahydronaphthyridine-N-dioxide, perhydronaphthyridine,perhydronaphthyridine-N-monoxide, perhydronaphthyridine-N-dioxide,dihydroquinoxaline, dihydroquinoxaline-N-monoxide,dihydroquinoxaline-N-dioxide, tetrahydroquinoxaline,tetrahydroquinoxaline-N-monoxide, tetrahydroquinoxaline-N-dioxide,perhydroquinoxaline, perhydroquinoxaline-N-monoxide,perhydroquinoxaline-N-dioxide, dihydroquinazoline,dihydroquinazoline-N-monoxide, dihydroquinazoline-N-dioxide,tetrahydroquinazoline, tetrahydroquinazoline-N-monoxide,tetrahydroquinazoline-N-dioxide, perhydroquinazoline,perhydroquinazoline-N-monoxide, perhydroquinazoline-N-dioxide,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzoimidazole, perhydrobenzoimidazole,benzoxazepine, benzoxadiazepine, benzothiazepine, benzothiadiazepine,benzoazepine, benzodiazepine, indroxoazepine, indrotetrahydroxazepine,indroxadiazepine, indrotetrahydroxadiazepine, indrothiazepine,indrotetrahydrothiazepine, indrothiadiazepine,indrotetrahydrothiadiazepine, indroazepine, indrotetrahydroazepine,indrodiazepine, indrotetrahydrodiazepine, benzofurazane,benzothiadiazole, benzotriazole, camphar, imidazothiazole,dihydrocarbazole, tetrahydrocarbazole, perhydrocarbazole,dihydroacridine, tetrahydroacridine, perhydroacridine, 1,3-dioxaindan,1,4-dioxoindan ring etc.

[0439] In the present invention, m is, preferably, 0 or 2 and mostpreferably, 2.

[0440] n is, preferably, 0 or 2 and most preferably, 2.

[0441] p is, preferably, 1 or 2 and most preferably, 2.

[0442] q is, preferably, 0 or 1.

[0443] Z is, preferably, single bond or C1-8 alkylene, and mostpreferably, single bond.

[0444] is, preferably, pyridine or benzene ring, and most preferably,benzene ring.

[0445] is, preferably, C5-10 mono- or bicyclic carbo ring or 5-10membered mono- or bicyclic hetero ring containing 1-3 nitrogen atom(s),one oxygen atom and/or one sulfur atom, more preferably, benzene,cyclohexane, thiophene, furan, pyridine, pyrimizine, imidazole ring, andmost preferably, benzene or thiophene ring.

[0446] R¹ is, preferably, C1-8 alkyl, nitro, cyano, halogen, Cyc¹ orC1-8 alkyl substituted with halogen or Cyc¹, or A¹—A²—A³, and mostpreferably, C1-8 alkyl substituted with Cyc¹ or A¹—A²—A³.

[0447] A¹ is, preferably, single bond, C1-8 alkylene, C2-8 alkenylene,and most preferably, single bond or C1-8 alkylene.

[0448] A² is, preferably, —O—, —NR³—, —C(O)—, —C(O)NR⁴—, —NR⁵C(O)—,—C(O)O—, —NR¹³C(O)O—, and most preferably, O—, —NR³—, —C(O)—, —C(O)NR⁴—,—NR⁵C(O)—.

[0449] A³ is, preferably, C1-8 alkyl, Cyc¹, or C1-8 alkyl or C2-8alkenyl substituted with Cyc¹, —C(O)R ⁷, —NR¹⁹R²⁰ or —OR¹⁸, and mostpreferably, C1-8 alkyl substituted with Cyc¹ or NR¹⁹R²⁰.

[0450] Cyc¹ is, preferably, C5-10 mono- or bicyclic carbo ring or 5-10membered mono- or bicyclic hetero ring containing 1-3 nitrogen atom(s),one oxygen atom and/or one sulfur atom, and more preferably, C5-10monocyclic carbo ring or 5-10 membered monocyclic hetero ring containing1-2 nitrogen atom(s) and/or one oxygen atom, and most preferably,benzene, piperidine, piperazine, pyrrolidine, pyridine or morpholinering.

[0451] R¹⁹, R²⁰ is, preferably, hydrogen or C1-8 alkyl, and mostpreferably, methyl, ethyl, propyl or isopropyl.

[0452] [Salts]

[0453] In the present invention, non-toxic salts include all such salts,for example, ordinal salts, acid-addition salts and hydrate salts.

[0454] The compounds of the present invention of the formula (I) may beconverted into the corresponding salts by known method. Non toxic andwater-soluble salts are preferable. Suitable salts include the salts ofalkalimetal (sodium, potassium etc.), alkaline-earth metal (calcium,magnesium etc.), ammonium salts, salts of organic amine which ispharmaceutically permitted (tetramethyl ammonium, triethylamine,methylamine, dimethylamine, cyclopentylamine, benzylamine,phenetylamine, piperidine, monoethanolamine, diethanolamine,tris(hydroxymethyl)amine, lysine, arginine, N-methyl-D-gulcamine etc.).

[0455] The compounds of the present invention of the formula (I) may beconverted into the corresponding acid-addition salts by known method.Non toxic and water-soluble acid-addition are preferable. Suitableacid-addition salts include the salts with inorganic acids such ashydrochloric acid, hydrobromic acid, sulfonic acid, phosphonic acid,nitric acid and the salts with organic acids such as acetic acid,trifluoroacetic acid, lactic acid, tartaric acid, oxalic acid, fumaricacid, maleic acid, citric acid, benzoic acid, methanesulfonic acid,ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid,isethionic acid, glucuronic acid and gluconic acid.

[0456] The compounds of the present invention of the formula (I) orsalts thereof may be converted into a corresponding hydrate by knownmethods.

[0457] In the compounds of the formula (I), preferred compounds are asfollows: the compound of the formula (I-A)

[0458] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-B)

[0459] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-C)

[0460] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-D)

[0461] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-E)

[0462] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-F)

[0463] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-G)

[0464] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-H)

[0465] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-J)

[0466] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-K)

[0467] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-L)

[0468] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-M)

[0469] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-N)

[0470] (wherein all the symbols are the same meanings as hereinbeforedescribed.), the compound of the formula (I-O)

[0471] (wherein all the symbols are the same meanings as hereinbeforedescribed.), or the compound of the formula (I-P)

[0472] (wherein all the symbols are the same meanings as hereinbeforedescribed.).

[0473] In the compounds of the formula (I-A), the compound of theformula (I-A′)

[0474] (wherein, R^(1′) is C1-8 alkyl substituted with Cyc¹, or

[0475] (wherein, A^(1′) is single bond or C1-8 alkylene, A²′ is —O—,—NR³—, —C(O)—, —C(O)NR⁴— or NR⁵C(O)— and the other symbols are the samemeanings as hereinbefore described.) and the other symbols are the samemeanings as hereinbefore described.) is most preferable.

[0476] In the compound of the formula (I-N), the compound of the formula(I-N′)

[0477] (wherein all the symbols are the same meanings as hereinbeforedescribed.) is most preferable.

[0478] The following compounds (1)-(4) are known and marketed ones, buttheir activities as inhibitor of producing IL-6 and/or IL-12 have notbeen known at all. The compounds (1)-(4) and non-toxic salts thereof arealso preferable ones used in the present invention.

[0479] For example,

[0480] Compound (1):3-(thiophene-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene(Maybridge, Catalog No. KM 08156):

[0481] Compound (2):6-nitro-3-(thiophene-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene(Maybridge, Catalog No. KM 08165):

[0482] Compound (3): 3-(thiophene-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08138):

[0483] Compound (4):3-phenylsulfonyl-2,3-dihydro-11-dioxidebenzo[b]thiophene (Maybridge,Catalog No. KM 08140):

[0484] More preferable compounds are the following known compounds andthe compounds shown in the Tables 1 to 78 and described in Examples andnon-toxic salts thereof.

[0485] In the following tables, 3-Py is pyridin-3-yl, Me is methyl, Etis ethyl, n-Pr is normalpropyl, i-Pr is isopropyl, t-Bu is t-butyl andthe other symbols are the same meanings as hereinbefore described. TABLE1 (I-A)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 1 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 1 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 3′—O—(CH₂)₂-(3-Py) 11 0 — — 1 4′ —O—(CH₂)₂-(3-Py) 12 0 — — 2 3′, 5′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 3′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 4′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 2 3′, 5′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 4′—O—(CH₂)₂-(3-Py) 20 1 7 —O—(CH₂)₂-(3-Py) 2 3′, 5′ —O—(CH₂)₂-(3-Py)

[0486] TABLE 2 (I-B)

No. p position R¹ q position R² 1 1 5 —O—(CH₂)₂-(3-Py) 0 — — 2 1 6—O—(CH₂)₂-(3-Py) 0 — — 3 1 7 —O—(CH₂)₂-(3-Py) 0 — — 4 2 6, 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 5 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 6—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 7 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 2 6, 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 3′—O—(CH₂)₂-(3-Py) 11 0 — — 1 4′ —O—(CH₂)₂-(3-Py) 12 0 — — 2 3′, 5′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 3′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 4′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 2 3′, 5′—O—(CH₂)₂—N(CH₃)₂ 17 1 5 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 6—O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 19 1 7 —O—(CH₂)₂-(3-Py) 1 4′—O—(CH₂)₂-(3-Py) 20 2 6, 7 —O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py)

[0487] TABLE 3 (I-C)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 2 4, 5—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 2 4, 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 3′—O—(CH₂)₂-(3-Py) 11 0 — — 1 4′ —O—(CH₂)₂-(3-Py) 12 0 — — 2 3′, 5′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 3′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 4′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 2 3′, 5′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 4′—O—(CH₂)₂-(3-Py) 20 2 4, 5 —O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py)

[0488] TABLE 4 (I-D)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 1 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 1 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 3′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 4′—O—(CH₂)₂-(3-Py) 11 0 — — 1 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 1 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 3′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 4′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 1 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 4′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 5′—O—(CH₂)₂-(3-Py) 20 1 7 —O—(CH₂)₂-(3-Py) 1 6′ —O—(CH₂)₂-(3-Py)

[0489] TABLE 5 (I-E)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 1 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 1 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 4′—O—(CH₂)₂-(3-Py) 11 0 — — 1 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 1 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 4′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 1 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 4′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 5′—O—(CH₂)₂-(3-Py) 20 1 7 —O—(CH₂)₂-(3-Py) 1 6′ —O—(CH₂)₂-(3-Py)

[0490] TABLE 6 (I-F)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 1 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 1 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 3′—O—(CH₂)₂-(3-Py) 11 0 — — 2 2′, 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 2 2′, 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 3′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 2 2′, 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 2 2′, 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 2′—O—(CH₂)₂-(3-Py) 20 1 7 —O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py)

[0491] TABLE 7 (I-G)

No. p position R¹ q position R² 1 1 5 —O—(CH₂)₂-(3-Py) 0 — — 2 1 6—O—(CH₂)₂-(3-Py) 0 — — 3 1 7 —O—(CH₂)₂-(3-Py) 0 — — 4 2 6, 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 5 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 6—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 7 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 2 6, 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 3′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 4′—O—(CH₂)₂-(3-Py) 11 0 — — 1 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 1 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 3′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 4′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 1 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 5 —O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 18 1 6—O—(CH₂)₂-(3-Py) 1 4′ —O—(CH₂)₂-(3-Py) 19 1 7 —O—(CH₂)₂-(3-Py) 1 5′—O—(CH₂)₂-(3-Py) 20 2 6, 7 —O—(CH₂)₂-(3-Py) 1 6′ —O—(CH₂)₂-(3-Py)

[0492] TABLE 8 (I-H)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 2 4, 5—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 2 4, 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 3′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 4′—O—(CH₂)₂-(3-Py) 11 0 — — 1 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 1 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 3′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 4′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 1 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 4′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 5′—O—(CH₂)₂-(3-Py) 20 2 4, 5 —O—(CH₂)₂-(3-Py) 1 6′ —O—(CH₂)₂-(3-Py)

[0493] TABLE 9 (I-J)

No. p position R¹ q position R² 1 1 5 —O—(CH₂)₂-(3-Py) 0 — — 2 1 6—O—(CH₂)₂-(3-Py) 0 — — 3 1 7 —O—(CH₂)₂-(3-Py) 0 — — 4 2 6, 7—O—(CH₂)₂-(3-Py) 0 — — 5 1 5 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 6—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 7 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 2 6, 7—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 4′—O—(CH₂)₂-(3-Py) 11 0 — — 1 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 1 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 4′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 1 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 5 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 6—O—(CH₂)₂-(3-Py) 1 4′ —O—(CH₂)₂-(3-Py) 19 1 7 —O—(CH₂)₂-(3-Py) 1 5′—O—(CH₂)₂-(3-Py) 20 2 6, 7 —O—(CH₂)₂-(3-Py) 1 6′ —O—(CH₂)₂-(3-Py)

[0494] TABLE 10 (I-K)

No. p position R¹ q position R² 1 1 4 —O—(CH₂)₂-(3-Py) 0 — — 2 1 5—O—(CH₂)₂-(3-Py) 0 — — 3 1 6 —O—(CH₂)₂-(3-Py) 0 — — 4 2 4, 5—O—(CH₂)₂-(3-Py) 0 — — 5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — — 6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — — 8 2 4, 5—O—(CH₂)₂—N(CH₃)₂ 0 — — 9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 4′—O—(CH₂)₂-(3-Py) 11 0 — — 1 5′ —O—(CH₂)₂-(3-Py) 12 0 — — 1 6′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 4′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 1 5′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 1 6′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 4′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 1 5′—O—(CH₂)₂-(3-Py) 20 2 4, 5 —O—(CH₂)₂-(3-Py) 1 6′ —O—(CH₂)₂-(3-Py)

[0495] TABLE 11 (I-L)

No. p position R¹ q position R²  1 1 5 —O—(CH₂)₂-(3-Py) 0 — —  2 1 6—O—(CH₂)₂-(3-Py) 0 — —  3 1 7 —O—(CH₂)₂-(3-Py) 0 — —  4 2 6, 7—O—(CH₂)₂-(3-Py) 0 — —  5 1 5 —O—(CH₂)₂—N(CH₃)₂ 0 — —  6 1 6—O—(CH₂)₂—N(CH₃)₂ 0 — —  7 1 7 —O—(CH₂)₂—N(CH₃)₂ 0 — —  8 2 6, 7—O—(CH₂)₂—N(CH₃)₂ 0 — —  9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 3′—O—(CH₂)₂-(3-Py) 11 0 — — 2 2′, 3′ —O—(CH₂)₂-(3-Py) 12 0 — — 2 2′, 5′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 3′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 2 2′, 3′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 2 2′, 5′—O—(CH₂)₂—N(CH₃)₂ 17 1 5 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 6—O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 19 1 7 —O—(CH₂)₂-(3-Py) 2 2′, 3′—O—(CH₂)₂-(3-Py) 20 2 6, 7 —O—(CH₂)₂-(3-Py) 2 2′, 5′ —O—(CH₂)₂-(3-Py)

[0496] TABLE 12 (I-M)

No. p position R¹ q position R²  1 1 4 —O—(CH₂)₂-(3-Py) 0 — —  2 1 5—O—(CH₂)₂-(3-Py) 0 — —  3 1 6 —O—(CH₂)₂-(3-Py) 0 — —  4 2 4, 5—O—(CH₂)₂-(3-Py) 0 — —  5 1 4 —O—(CH₂)₂—N(CH₃)₂ 0 — —  6 1 5—O—(CH₂)₂—N(CH₃)₂ 0 — —  7 1 6 —O—(CH₂)₂—N(CH₃)₂ 0 — —  8 2 4, 5—O—(CH₂)₂—N(CH₃)₂ 0 — —  9 0 — — 1 2′ —O—(CH₂)₂-(3-Py) 10 0 — — 1 3′—O—(CH₂)₂-(3-Py) 11 0 — — 2 2′, 3′ —O—(CH₂)₂-(3-Py) 12 0 — — 2 2′, 5′—O—(CH₂)₂-(3-Py) 13 0 — — 1 2′ —O—(CH₂)₂—N(CH₃)₂ 14 0 — — 1 3′—O—(CH₂)₂—N(CH₃)₂ 15 0 — — 2 2′, 3′ —O—(CH₂)₂—N(CH₃)₂ 16 0 — — 2 2′, 5′—O—(CH₂)₂—N(CH₃)₂ 17 1 4 —O—(CH₂)₂-(3-Py) 1 2′ —O—(CH₂)₂-(3-Py) 18 1 5—O—(CH₂)₂-(3-Py) 1 3′ —O—(CH₂)₂-(3-Py) 19 1 6 —O—(CH₂)₂-(3-Py) 2 2′, 3′—O—(CH₂)₂-(3-Py) 20 2 4, 5 —O—(CH₂)₂-(3-Py) 2 2′, 5′ —O—(CH₂)₂-(3-Py)

[0497] TABLE 13 (I-A-1)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0498] TABLE 14 (I-A-2)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0499] TABLE 15 (I-A-3)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0500] TABLE 16 (I-A-4)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0501] TABLE 17 (I-B-1)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0502] TABLE 18 (I-B-2)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0503] TABLE 19 (I-B-3)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0504] TABLE 20 (I-C-1)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0505] TABLE 21 (I-C-2)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0506] TABLE 22 (I-C-3)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0507] TABLE 23 (I-D-1)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0508] TABLE 24 (I-D-2)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0509] TABLE 25 (I-D-3)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0510] TABLE 26 (I-D-4)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0511] TABLE 27 (I-E-1)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0512] TABLE 28 (I-E-2)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0513] TABLE 29 (I-E-3)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0514] TABLE 30 (I-E-4)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0515] TABLE 31

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0516] TABLE 32

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0517] TABLE 33

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0518] TABLE 34

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0519] TABLE 35

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0520] TABLE 36

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0521] TABLE 37

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0522] TABLE 38

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0523] TABLE 39

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0524] TABLE 40

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0525] TABLE 41

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0526] TABLE 42

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0527] TABLE 43

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0528] TABLE 44

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0529] TABLE 45

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0530] TABLE 46

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0531] TABLE 47

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0532] TABLE 48

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0533] TABLE 49

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0534] TABLE 50

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0535] TABLE 51 (I-M-2)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0536] TABLE 52 (I-M-3)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0537] TABLE 53 (I-N-1)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0538] TABLE 54 (I-N-2)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0539] TABLE 55 (I-N-3)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0540] TABLE 56 (I-N-4)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0541] TABLE 57 (I-O-1)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0542] TABLE 58 (I-O-2)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0543] TABLE 59 (I-O-3)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0544] TABLE 60 (I-P-1)

No. R¹ No. R¹ 1

11

2

12

3

13

4

14

5

15

6

16

7

17

8

18

9

19

10 

20

[0545] TABLE 61 (I-P-2)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0546] TABLE 62 (I-P-3)

No. R¹ 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

[0547] TABLE 63 (I-A-1)

No. R¹ 21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

[0548] TABLE 64 (I-A-1)

No. R¹ 45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

[0549] TABLE 65 (I-A-2)

No. R¹ 21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

[0550] TABLE 66 (I-A-2)

No. R¹ 45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

[0551] TABLE 67 (I-A-3)

No. R¹ 21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

[0552] TABLE 68 (I-A-3)

No. R¹ 45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

[0553] TABLE 69 (I-A-4)

No. R¹ 21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

[0554] TABLE 70 (I-A-4)

No. R¹ 45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

[0555] TABLE 71 (I-N-1)

No. R¹ No. R¹ 21

33

22

34

23

35

24

36

25

37

26

38

27

39

28

40

29

41

30

42

31

43

32

44

[0556] TABLE 72 (I-N-1)

No. R¹ No. R¹ 45

57

46

58

47

59

48

60

49

61

50

62

51

63

52

64

53

65

54

66

55

67

56

[0557] TABLE 73 (I-N-2)

No. R¹ No. R¹ 21

33

22

34

23

35

24

36

25

37

26

38

27

39

28

40

29

41

30

42

31

43

32

44

[0558] TABLE 74 (I-N-2)

No. R¹ No. R¹ 45

57

46

58

47

59

48

60

49

61

50

62

51

63

52

64

53

65

54

66

55

67

56

[0559] TABLE 75 (I-N-3)

No. R¹ No. R¹ 21

33

22

34

23

35

24

36

25

37

26

38

27

39

28

40

29

41

30

42

31

43

32

44

[0560] TABLE 76 (I-N-3)

No. R¹ No. R¹ 45

57

46

58

47

59

48

60

49

61

50

62

51

63

52

64

53

65

54

66

55

67

56

[0561] TABLE 77 (I-N-4)

No. R¹ No. R¹ 21

33

22

34

23

35

24

36

25

37

26

38

27

39

28

40

29

41

30

42

31

43

32

44

[0562] TABLE 78 (I-N-4)

No. R¹ No. R¹ 45

57

46

58

47

59

48

60

49

61

50

62

51

63

52

64

53

65

54

66

55

67

56

[0563] [Methods for Preparation of the Compounds of the PresentInvention]

[0564] The compounds of the present invention of the formula (I) of thepresent invention may be prepared by the following methods or themethods described in examples.

[0565] Among the compounds of the present invention of the formula (I),the compounds of the present invention of the formula (I-1)

[0566] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by the known methods or the followingmethods [1]˜14].

[0567] [1] The compounds of the present invention of the formula (I-1)in which n is 1 or 2 may be also prepared by the following methods(a)˜(b).

[0568] (a) The compounds of the present invention of the formula (I-1)in which n is 1, i.e., the compounds of the present invention of theformula (I-1-1a)

[0569] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by oxidation of the compounds of the formula(I-1-1c)

[0570] (wherein all the symbols are the same meanings as hereinbeforedescribed.)

[0571] The above oxidation is known per se. For example, it may becarried out in an adequate organic solvent (e.g., methylene chloride,chloroform, benzene, hexane, t-butyl alcohol etc.), in the presence ofan 1-1.2 equivalent amount of oxidizing agent (e.g., hydrogen peroxide,sodium periodate, acyl nitrite, sodium perborate, peracid (e.g.,3-chloroperbenzoic acid, peracetic acid etc.), potassiumperoxymonosulfate, potassium permanganate, chromic acid etc.), at -40°C.˜0° C.

[0572] (b) The compounds of the present invention of the formula (I-1)in which n is 2, i.e., the compounds of the present invention of theformula (I-1-1b)

[0573] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by oxidation of the said the compounds ofthe formula (I-1-1c).

[0574] The above oxidation is known per se. For example, it may becarried out in an adequate organic solvent (e.g., methylene chloride,chloroform, benzene, hexane, t-butyl alcohol etc.), in the presence ofan excess amount of oxidizing agent (e.g., hydrogen peroxide, sodiumperiodate, acyl nitrite, sodium perborate, peracid (e.g.,3-chloroperbenzoic acid, peracetic acid etc.), potassiumperoxymonosulfate, potassium permanganate, chromic acid etc.), at 20°C.˜60° C.

[0575] [2] The compounds of the present invention of the formula (I-1)in which at least one of R¹ (s) is a substituted oxy group or a groupcontaining substituted oxy, i.e., the compounds of the present inventionof the formula (I-1-2)

[0576] (wherein, R¹⁻¹⁻² is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R¹⁻¹⁻²(s) is a substituted oxygroup or a group containing substituted oxy and the other symbols arethe same meaning as hereinbefore described.)

[0577] may be also prepared by the following methods (a)˜(b).

[0578] (a) The compounds of the present invention of the formula (I-1-2)may be prepared by etherification of the compounds of the formula (I-1-2) in which at least one of R¹(s) is a hydroxy or a group containinghydroxy, i.e., the compounds of the formula (I-1-2a)

[0579] (wherein, R R^(1-1-2a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R^(1-1-2a)(s) is ahydroxy or a group containing hydroxy and the other symbols are the samemeaning as hereinbefore described.) with the corresponding compoundscontaining a group which is removal (chloride, bromide, iodide, mesyl ortosyl etc.).

[0580] This etherification is well known. For example, it may be carriedout in an organic solvent (dimethylformamide, dimethylsulfoxide,chloroform, methyhlene chloride, diethyl ether, tetrahydrofuran etc.) inthe presence of hydroxide of an alkalimetal (sodium hydroxide, potassiumhydroxide, lithium hydroxide etc.), hydroxide of an alkaline earth metal(barium hydroxide, calcium hydroxide etc.) or carbonate (sodiumcarbonate , potassium carbonate etc.) or an aqueous solution thereof ora mixture thereof at 0˜100° C.

[0581] (b) The compounds of the present invention of the formula (I-1-2)may be prepared by etherification of the compounds of the formula (1-1-2) in which at least one of R¹(s) is a hydroxy or a group containinghydroxy, i.e., the compounds of the formula (I-1-2b)

[0582] (wherein, R R^(1-1-2b) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R^(1-1-2b)(s) is ahydroxy or a group containing hydroxy and the other symbols are the samemeaning as hereinbefore described.) with the corresponding compoundscontaining hydroxy.

[0583] This etherification is well known. For example, it may be carriedout in an organic solvent (methylene chloride, diethyl ether,tetrahydrofuran, acetonitrile, benzene, toluene etc.) in the presence ofazo compounds (diethyl azodicaroxylate, diisopropyl azodicaroxylate,1,1′-(azodicarbonyl)dipiperidine, 1,1′-azobis(N,N-dimethylformamide)etc.) and phosphine compounds (triphenylphosphine , tributylphosphine ,trimethylphosphine etc.), with the corresponding alcohol compounds at0˜60° C.

[0584] [3] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted amino or a groupcontaining substituted amino, i.e., the compounds of the presentinvention of the formula (I-1-3)

[0585] (wherein, R¹⁻¹⁻³ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R¹⁻¹⁻³(s) is a substituted aminoor a group containing substituted amino and the other symbols are thesame meaning as hereinbefore described.)

[0586] may be prepared by the following methods (a)˜(d).

[0587] (a) The compounds of the present invention of the formula (I-1-3)may be prepared by reacting the compounds of the formula (I-1-3) inwhich at least one of R¹(s) is halogen (chloride, bromide, iodide) or agroup containing halogen, i.e., the compounds of the formula (I-1-3a)

[0588] (wherein, R R¹⁻¹⁻³ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R^(1-1-3a)(s) is a halogen(chloride, bromide, iodide) or a group containing halogen and the othersymbols are the same meaning as hereinbefore described.)

[0589] and the corresponding compounds containing amino.

[0590] This reaction is well known. For example, it may be carried outin an organic solvent (dimethylformamide, dimethylsulfoxide, chloroform,methyhlene chloride, diethyl ether, tetrahydrofuran, acetonitrile etc.)in the presence or absence of base (triethylamine, pyridine etc.) at0˜100° C.

[0591] (b) The compounds of the present invention of the formula (I-1-3)may be prepared by reacting the compounds of the formula (I-1-3) inwhich at least one of R¹(s) is an amino or a group containing amino,i.e., the compounds of the formula (I-1-3b)

[0592] (wherein, R R^(1-1-3b) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R^(1-1-3b)(s) is anamino or a group containing amino and the other symbols are the samemeaning as hereinbefore described.) and the corresponding compoundscontaining halogen (chloride, bromide, and iodide).

[0593] This reaction may be carried out by the same procedure for thepreparation of the said compounds of the formula (I-1-3a).

[0594] (c) The compounds of the present invention of the formula (I-1-3)may be prepared by reductive amidation of the compounds of the formula(I-1-3) in which at least one of R¹(s) is an amino or a group containingamino, i.e., the compounds of the formula (I-1-3c)

[0595] (wherein, R R^(1-1-3c) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R¹⁻¹⁻³(s) is an aminoor a group containing amino and the other symbols are the same meaningas hereinbefore described.) with the corresponding compounds containingcarbonyl.

[0596] This reductive amidation is well known. For example, it may becarried out in an organic solvent (methanol, ethanol, dimethylformamide,dimethylsulfoxide etc,) in the presence of reductant (sodiumcyanoborohydride, sodium triacetoxyborohydride, sodium borohydride, Pd-Cetc.) and in the presence of acid (acetic acid, hydrochlolride solutionetc.), if necessary, at −20˜60° C.

[0597] (d) The compounds of the present invention of the formula (I-1-3)may be prepared by reductive amidation of the compounds of the formula(I-1-3) in which at least one of R¹(s) is a carbonyl or a groupcontaining carbonyl, i.e., the compounds of the formula (I-1-3d)

[0598] (wherein, R R^(1-1-3d) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R^(1-1-3d)(s) is acarbonyl or a group containing carbonyl and the other symbols are thesame meaning as hereinbefore described.)

[0599] with the corresponding compounds containing amino.

[0600] This reductive amidation may be carried out by the same procedurefor preparation of the said compounds of the formula (I-1-3c).

[0601] [4] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is an amide or a group containing amide,i.e., the compounds of the present invention of the formula (I-1-4)

[0602] (wherein, R¹⁻¹⁻⁴ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R¹⁻¹⁻⁴(s) is an amide or a groupcontaining amide and the other symbols are the same meaning ashereinbefore described.) may be prepared by the following methods(a)˜(b).

[0603] (a) The compounds of the present invention of the formula (I-1-4)may be prepared by amidation of the compounds of the formula (I-1) inwhich at least one of R¹(s) is a —COOH or a group containing —COOH,i.e., the compounds of the formula (I-1-4a)

[0604] (wherein, R R^(1-1-4a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R^(1-1-4a)(s) is a—COOH or a group containing —COOH and the other symbols are the samemeaning as hereinbefore described.) with the corresponding compoundscontaining amino.

[0605] The amidation is well known. For example, it may be carried out

[0606] (1) by the method with using acid halide,

[0607] (2) by the method with using mixed acid anhydride,

[0608] (3) by the method with using conducing agent etc.

[0609] Concrete description of these methods are as follows:

[0610] (1) method with using acid halide may be carried out, forexample; carboxylic acid is reacted with an acid halide (oxalyl chlorideor thionyl chloride etc.) in an organic solvent (chloroform, methylenechloride, diethyl ether or tetrahydrofuran etc.) or without solvents atfrom −20° C. to a refluxing temperature to give an acid halide. Theobtained acid halide and an amine are reacted in an organic solvent(chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.) inthe presence of tertiary amine (pyridine, triethylamine, dimethylanilineor dimethylaminopyridine etc.) at 0-40° C.

[0611] (2) method with using mixed acid anhydride may be carried out,for example; carboxylic acid is reacted with an acid halide (pivaloylchloride, tosyl chloride, mesyl chloride etc.) or an acid derivative(ethyl chloroformate, isobutyl chloroformate etc.) in an organic solvent(chloroform, methylene chloride, diethyl ether, tetrahydrofuran. etc.)or without solvents, in the presence of tertiary amine (pyridine,triethylamine, dimethylaniline or dimethylaminopyridine etc.), at 0-40°C.

[0612] (3) method with using condensing agent may be carried out, forexample; a carboxylic acid and an amine are reacted in an organicsolvent (chloroform, methylene chloride, dimethylformamide, diethylether or tetrahydrofuran. etc.) or without solvents in the presence orabsence of tertiary amine (pyridine, triethylamine, dimethylaniline ordimethylaminopyridine etc.) using with condensing agent(1,3-dicyclohexylcarbodiimido (DCC),1-ethyl-3-[3-(dimethylamino)propyl]carbodiimido (EDC),1,1′-carbonydimidazole (CDI), 2-chloro-1-methylpyridinium iodide,propane phosphate cyclic anhydride etc.) using or without1-hydroxybenztriazole (HOBt) at 0-40° C. (etc.)

[0613] Preferably, the above reactions (1), (2) and (3) described aboveare carried out under an atmosphere of an inert gas (argon, nitrogenetc.) on anhydrous condition.

[0614] (b) The compounds of the present invention of the formula (I-1-4)may be prepared by amidation of the compounds of the formula (I-1) inwhich at least one of R¹(s) is an amino or a group containing amino,i.e., the compounds of the formula (I-1-4b)

[0615] (wherein, R R^(1-1-4b) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R R^(1-1-4b)(s) is anamino or a group containing amino and the other symbols are the samemeaning as hereinbefore described.)with the corresponding compoundscontaining carboxy.

[0616] The above amidation may be carried out by the same procedure forpreparation of the said compounds of the formula (I-1-4a).

[0617] [5] The compounds of the present invention of the formula (1-1)in which at least one of R¹(s) is an ester or a group containing ester,i.e., the compounds of the present invention of the formula (I-1-5)

[0618] (wherein, R¹⁻¹⁻⁵ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻⁵(s) is an ester or a groupcontaining ester and the other symbols are the same meaning ashereinbefore described.) may be prepared by the following methods(a)˜(b).

[0619] (a) The compounds of the present invention of the formula (I-1-5)may be prepared by esterification of the compounds of the formula (I-1)in which at least one of R¹(s) is a —COOH or a group containing —COOH,i.e., the compounds of the formula (I-1-5a)

[0620] (wherein, R^(1-1-5a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-5a)(s) is a —COOHor a group containing —COOH and the other symbols are the same meaningas hereinbefore described.) with the corresponding compounds containinghydroxy.

[0621] Esterification is well known. For example, it may be carried out

[0622] (1) by the method with using acid halide,

[0623] (2) by the method with using mixed acid anhydride,

[0624] (3) by the method with using conducing agent etc.

[0625] Concrete description of the above methods are as follows:

[0626] (1) method with using acid halide may be carried out, forexample; carboxylic acid is reacted with an acid halide (oxalyl chlorideor thionyl chloride -etc.) in an inert organic solvent (chloroform,methylene chloride, diethyl ether or tetrahydrofuran etc.) or withoutsolvents at from −20° C. to a refluxing temperature to give an acidhalide. The obtained acid halide and an alcohol are reacted in an inertorganic solvent (chloroform, methylene chloride, diethyl ether,tetrahydrofuran etc.) in the presence of tertiary amine (pyridine,triethylamine, dimethylaniline or dimethylaminopyridine etc.) at 0-40°C.

[0627] (2) method with using mixed acid anhydride may be carried out,for example; carboxylic acid is reacted with an acid halide (pivaloylchloride, tosyl chloride, mesyl chloride etc.) or an acid derivative(ethyl chloroformate, isobutyl chloroformate etc.) in an inert organicsolvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran.etc.) or without solvents, in the presence of tertiary amine (pyridine,triethylamine, dimethylaniline or dimethylaminopyridine etc.), at 0-40°C. to give an acid halide. The obtained acid halide and an alcohol arereacted in an inert organic solvent (chloroform, methylene chloride,diethyl ether, tetrahydrofuran etc.) at 0-40° C.

[0628] (3) method with using condensing agent may be carried out, forexample; a carboxylic acid and an alcohol are reacted in an organicsolvent (chloroform, methylene chloride, dimethylformamide, diethylether or tetrahydrofuran. etc.) or without solvents in the presence orabsence of tertiary amine (pyridine, triethylamine, dimethylaniline ordimethylaminopyridine etc.) using with condensing agent(1,3-dicyclohexylcarbodiimido (DCC),1-ethyl-3-[3-(dimethylamino)propyl]carbodiimido (EDC),1,1′-carbonydimidazole (CDI), 2-chloro-1-methylpyridinium iodide,propane phosphate cyclic anhydride etc.) using or without1-hydroxybenztriazole (HOBt) at 0-40° C.

[0629] Preferably, the reactions (1), (2) and (3) described above arecarried out under an atmosphere of inert gas (argon, nitrogen etc.) onanhydrous condition.

[0630] (b) The compounds of the present invention of the formula (1-1-5)may be prepared by esterification of the compounds of the formula (I-1)in which at least one of R¹(s) is a hydroxy or a group containinghydroxy, i.e., the compounds of the formula (I-1-5b)

[0631] (wherein, R^(1-1-5b) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-5b)(s) is ahydroxy or a group containing hydroxy and the other symbols are the samemeaning as hereinbefore described.) with the corresponding compoundscontaining carboxy.

[0632] The esterification may be carried out by the same procedure forpreparation of the said compounds of the formula (I-1-5a).

[0633] [6] The compounds of the present invention of the formula (1-1)in which at least one of R¹(s) is a sulfonamide or a group containingsulfonamide, i.e., the compounds of the present invention of the formula(I-1-6)

[0634] (wherein, R¹⁻¹⁻⁶ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻⁶(s) is a sulfonamide or agroup containing sulfonamide and the other symbols are the same meaningas hereinbefore described.) may be prepared by the following methods(a)˜(b).

[0635] (a) The compounds of the present invention of the formula (I-1-6)may be prepared by sulfonamidation of the compounds of the formula (I-1)in which at least one of R¹(s) is a —SO₃H or a group containing —SO₂H,i.e., the compounds of the formula (II)

[0636] (wherein, R^(1-1-6a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-6a)(s) is a —SO₃Hor a group containing —SO₃H and the other symbols are the same meaningas hereinbefore described.) with the corresponding compounds containingamino.

[0637] The sulfonamidation is well known. For example, it may be carriedout by reacting sulfonic acid with acid halide (oxazolyl chloride,thionyl chloride etc.) in an inert organic solvent (chloroform,methyhlene chloride, diethyl ether, tetrahydrofuran etc.) or withoutsolvent, at −20° C. refluxing temperature to obtain sulfonylhalide andthen by reacting the obtained sulfonylhalide with an amine in an inertorganic solvent (chloroform, methyhlene chloride, diethyl ether,tetrahydrofuran etc.) in the presence of tertiary amine (pyridine,triethylamine, dimethylaniline, dimethylaminopyridine etc.) at 0˜40° C.

[0638] (b) The compounds of the present invention of the formula (I-1-6)may be prepared by sulfonamidation of the compounds of the formula (1-1)in which at least one of R¹(s) is an amino or a group containing amino,i.e., the compounds of the formula (I-1-6b)

[0639] (wherein, R^(1-1-6b) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-6b)(s) is anamino or a group containing amino and the other symbols are the samemeaning as hereinbefore described.) with the corresponding compoundscontaining sulfo.

[0640] The sulfonamidation may be carried out the same procedure forpreparation of the said compounds of the formula (I-1-6a).

[0641] [7] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted aminocarbonyloxy or agroup containing a substituted aminocarbonyloxy, i.e., the compounds ofthe present invention of the formula (I-1-7)

[0642] (wherein, R R¹⁻¹⁻⁷ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R¹⁻¹⁻⁷(s) is a substitutedaminocarbonyloxy or a group containing a substituted aminocarbonyloxyand the other symbols are the same meaning as hereinbefore described.)may be prepared by reacting the compounds of the formula (I-1) in whichat least one of R¹(s) is a hydroxy or a group containing hydroxy, i.e.,the compounds of the formula (I-1-7a)

[0643] (wherein, R^(1-1-7a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-7a)(s) is ahydroxy or a group containing hydroxy and the other symbols are the samemeaning as hereinbefore described.) with the corresponding compoundscontaining isocyanate.

[0644] This reaction is well known. For example, it may be carried outin an organic solvent (tetrahydrofuran, methyhlene chloride, diethylether etc.) in the presence of base (1,8-diazabicyclo[5.4.0]undec-7-en(DBU), triethylamine, sodium hydride etc.) at 0˜100° C.

[0645] [8] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted aminocarbonylamino or agroup containing a substituted aminocarbonylamino, i.e., the compoundsof the present invention of the formula (I-1-8)

[0646] (wherein, R¹⁻¹⁻⁸ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻⁸(s) is a substitutedaminocarbonyl or a group containing a substituted aminocarbonyl and theother symbols are the same meaning as hereinbefore described.) may beprepared by reacting the compounds of the formula (I-1) in which atleast one of R¹(s) is an amino or a group containing amino, i.e., thecompounds of the formula (I-1-8a)

[0647] (wherein, R R¹⁻¹⁻⁸ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R^(1-1-8a)(s) is an amino or agroup containing amino and the other symbols are the same meaning ashereinbefore described.) with the corresponding compounds containingisocyanate.

[0648] This reaction may be carried out by the same procedure forpreparation of the said compounds of the formula (I-1-7).

[0649] [9] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted oxycarbonylamino or agroup containing a substituted oxyocarbonylamino, i.e., the compounds ofthe present invention of the formula (I-1-9)

[0650] (wherein, R R¹⁻¹⁻⁹ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R¹⁻¹⁻⁹(s) is a substitutedoxycarbonylamino or a group containing a substituted oxyocarbonylaminoand the other symbols are the same meaning as hereinbefore described.)may be prepared by esterification of the compounds of the formula (I-1)in which at least one of R¹(s) is an amino or a group containing amino,i.e., the compounds of the formula (I-1-9a)

[0651] (wherein, R R^(1-1-9a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-9a)(s) is anamino or a group containing amino and the other symbols are the samemeaning as hereinbefore described.) with the corresponding halo formicacid ester.

[0652] This reaction is well known. For example, it may be carried outin an organic solvent (tetrahydrofuran, methyhlene chloride, diethylether etc.) in the presence of base (triethylamine, pyridine etc.) at−78˜40° C.

[0653] [10] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted oxycarbonyloxy or agroup containing a substituted oxycarbonyloxy, i.e., the compounds ofthe present invention of the formula (I-1-10)

[0654] (wherein, R¹⁻¹⁻¹⁰ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻¹⁰(s) is a substitutedoxycarbonyloxy or a group containing a substituted oxycarbonyloxy andthe other symbols are the same meaning as hereinbefore described.) maybe prepared by esterification of the compounds of the formula (I-1) inwhich at least one of R¹(s) is a hydroxy or a group containing hydroxy,i.e., the compounds of the formula (I-1-10a)

[0655] (wherein, R^(1-1-10a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-10a)(s) is ahydroxy or a group containing hydroxy and the other symbols are the samemeaning as hereinbefore described.) with the corresponding halo formicacid ester.

[0656] This reaction may be carried out by the same procedure forpreparation of the said compounds of the formula (I-1-9).

[0657] [11] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted (hydroxy)methyl or agroup containing a substituted (hydroxy)methyl, i.e., the compounds ofthe present invention of the formula (I-1-11)

[0658] (wherein, R¹⁻¹⁻¹¹ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻¹¹(s) is a substituted(hydroxy)methyl or a group containing a substituted (hydroxy)methyl andthe other symbols are the same meaning as hereinbefore described.) maybe prepared by the following methods (a)˜(b).

[0659] (a) The compounds of the present invention of the formula(I-1-11) in which n is 0, i.e., the compounds of the present inventionof the formula (I-1-11a)

[0660] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by reacting the compounds of the formula(I-1) in which at least one of R¹(s) is a formyl i.e., the compounds ofthe formula (1-1-11 aa)

[0661] (wherein, R^(1-1-11aa) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-11a)(s) is aformyl and the other symbols are the same meaning as hereinbeforedescribed.)

[0662] with the corresponding Grignard's reagents or correspondingderivatives containing lithium.

[0663] This reaction is well known. For example, it may be carried outin an organic solvent (tetrahydrofuran, diethyl ether etc.) at −78˜0° C.

[0664] (b) The compounds of the present invention of the formula(I-1-11) in which n is 1 or 2, i.e., the compounds of the presentinvention of the formula (I-1-11b)

[0665] (wherein, n-1-11b is an integer of 1˜2 and the other symbols arethe same meaning as hereinbefore described.)

[0666] may be prepared by oxidizing the said compounds of the formula(I-1-11a) as described in [1].

[0667] [12] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a substituted carbonyl or a groupcontaining substituted carbonyformyl, i.e., the compounds of the presentinvention of the formula (I-1-12)

[0668] (wherein, R¹⁻¹⁻¹² is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻¹²(s) is an substitutedcarbonyl or a group containing substituted carbonyl and the othersymbols are the same meaning as hereinbefore described.)

[0669] may be prepared by oxidizing the said compounds of the formula(I-1-11).

[0670] This oxidation is well known. For example, it may be carried outin an organic solvent (methyhlene chloride, chloroform etc.) usingoxidant (manganese dioxide, oxazolyl chloride, pyridinium dichromateetc.) at −78˜40° C.

[0671] [13] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is an amino or a group containing amino,i.e., the compounds of the present invention of the formula (I-1 -13)

[0672] (wherein, R¹⁻¹⁻¹³ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R¹⁻¹⁻¹³(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) may be prepared by reducing nitro in thecompounds of the formula of (I-1) in which at least one of R¹(s) is anitro or a group containing nitro, i.e., the compounds of the formula(I-1-13a)

[0673] (wherein, R R^(1-1-13a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-13a)(s) is anitro or a group containing nitro and the other symbols are the samemeaning as hereinbefore described.).

[0674] The reduction of nitro is well known. For example, it may becarried out by hydrogenolysis and reduction using organic metal.

[0675] This hydrogenolysis is well known. For example, it may be carriedout in inert solvent [ethers (e.g., tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether etc.), alcohols (e.g., methanol , ethanol etc.),benzenes (e.g., benzene, toluene etc.), ketones (e.g., acetone, methylethyl ketone etc.), nitriles (e.g., acetonitrile etc.), amides (e.g.,dimethylformamide etc.), water, ethyl acetate, acetic acid or mixture ofthe said two or more solvents etc.], in the presence of catalyst tohydrogenate (e.g., Pd-C, palladium black, Pd, palladium hydroxide,platinum oxide, Ni, Raney nickel, ruthenium chloride etc.), in thepresence or absence of an inorganic acid (e.g., hydrochloric acid,sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboric acidetc.) or an organic acid (e.g., acetic acid, p-toluenesulfonic acid,bromic acid, trifluoroacetic acid, formic acid etc.), at an ordinary orincreased pressure under an atmosphere of hydrogen gas or in thepresence of ammonium formate at 0˜200° C. When an acid is used, its saltmay be used.

[0676] The reduction using an organic metal is well known. For example,it may be carried out in a water-admissible solvent (ethanol , methanoletc.) in the presence or absence of an aqueous hydrochloric acidsolution, using an organic metal (Zn, Fe, Sn, SnCl₂, FeCl₂ etc.) at50˜150° C.

[0677] [14] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) is a —COOH, hydroxy or amino or a groupcontaining —COOH, hydroxy or amino, i.e., the compounds of the presentinvention of the formula (I-1-14)

[0678] (wherein, R¹⁻¹⁻¹⁴ is the same meanings as hereinbefore describedfor R¹, provided that at least one of R R¹⁻¹⁻¹⁴(s) is a —COOH, hydroxyor amino or a group containing —COOH, hydroxy or amino and the othersymbols are the same meaning as hereinbefore described.) may be preparedby removal of protecting group in the compounds of the formula (I-1)containing a protected COOH, hydroxy or amino, i.e., the compounds ofthe formula (I-1-14a)

[0679] (wherein, R^(1-1-14a) is the same meanings as hereinbeforedescribed for R¹, provided that at least one of R^(1-1-14a)(s) is aprotected COOH (e.g., it is protected by methyl, ethyl, t-butyl andbenzyl etc.), protected hydroxy (e.g., it is protected by methoxymethyl,tetrahydropyranyl, t-butyldimethylsilyl, acetyl, benzyl etc.) orprotected amino (e.g., it is protected by benzyloxycarbonyl,t-butoxycarbonyloxy, trifluoroacetyl etc.) or a group containing such agroup, and the other symbols are the same meaning as hereinbeforedescribed.) according to alkaline hydrolysis, removal of protectinggroup in an acidic condition, removal of silyl or hydrogenolysis.

[0680] The removal of a protecting group according to alkalinehydrolysis is well known. For example, it may be carried out in anorganic solvent (methanol, tetrahydrofuran, dioxane etc.), usinghydroxide of an alkaline metal (sodium hydroxide, potassium hydroxide ,lithium hydroxide etc.), hydroxide of an alkaline earth metal (bariumhydroxide, calcium hydroxide etc.) or carbonate (sodium carbonate ,potassium carbonate etc.) or an aqueous solution thereof or a mixturethereof at 0˜40° C.

[0681] The removal of a protecting group in an acidic condition is wellknown. For example, it may be carried out in an organic solvent(methyhlene chloride, chloroform, dioxane, ethyl acetate, anisole etc.),organic acid (acetic acid, trifluoroacetic acid, methanesulfonic acid,trimethylsilyliodide etc.) or inorganic acid (hydrochloric acid,sulfuric acid etc.) or a mixture thereof (bromohydroacetic acid etc.) at0˜100° C.

[0682] The removal of silyl is well known. For example, it may becarried out in a water-admissible organic solvent (tetrahydrofuran,acetonitrile etc.), using tetrabutylammonium fluoride at 0˜40° C.

[0683] The removal of protecting group according to hydrogenolysis maybe carried out by the same procedure of hydrogenolysis described in[13].

[0684] Among the compounds of the formula (I), the compounds of theformula (I-2)

[0685] may be prepared by the following methods [15]˜[17].

[0686] [15] The compounds of the present invention of the formula (I-2)in which m is 0, i.e., the compounds of the present invention of theformula (I-2-15)

[0687] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by the following methods (a)˜(b).

[0688] (a) The compounds of the present invention of the formula(I-2-15) in which n is 1 or 2, i.e., the compounds of the presentinvention of the formula (I-2-15a)

[0689] (wherein, n-2-15a is an integer of 1˜2 and the other symbols arethe same meanings as hereinbefore described.) may be prepared byreacting the said compounds of the formula (I-1-1a) or the compounds ofthe formula (I-1-1b) and the compounds of the formula (III)

[0690] (wherein all the symbols are the same meanings as hereinbeforedescribed.).

[0691] This reaction is known one (to see J. Am. Chem. Soc., 72, 1985(1950), J. Org. Chem., 54, 4232 (1989). For example, it may be carriedout in an inert organic solvent (tetrahydrofuran, diethyl ether,methylene chloride, chloroform, benzene, toluene, dimethylformamide,dimethylsulfoxide, acetonitrile etc.) using hydride of an alkalinemetal, hydroxide of an alkaline metal (sodium hydroxide, potassiumhydroxide, lithium hydroxide etc.), hydroxide of an alkaline earth metal(barium hydroxide, calcium hydroxide etc.) or tertiary amine (pyridine,triethylamine, dimethylaniline, dimethylaminopyridine etc.) or anaqueous solution thereof, or a mixture thereof at 0˜40° C.

[0692] (b) The compounds of the present invention of the formula(I-2-15) in which n is 0, i.e., the compounds of the present inventionof the formula (I-2-15b)

[0693] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by reduction of the compounds obtained bythe. above mentioned method in which m is 0, n is 1, i.e., the compoundsof the formula (I-2-15ab)

[0694] (wherein all the symbols are the same meanings as hereinbeforedescribed.).

[0695] This reduction reaction is well known. For example, this reactionmay be carried out in an organic solvent (diethyl ether, tetrahydrofuranetc.) using reductant (lithium aluminum hydride, aluminumdiisobutylhydride etc.) at 0˜80° C.

[0696] [16] The compounds of the present invention of the formula (I-2)in which m is 1, i.e., the compounds of the present invention of theformula (I-2-16)

[0697] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by oxidizing the said compounds of theformula (I-2-15).

[0698] This oxidation may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-1a) in [1].

[0699] [17] The compounds of the present invention of the formula (I-2)in which m is 2, i.e., the compounds of the present invention of theformula (I-2-17)

[0700] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by the following methods (a)˜(c).

[0701] (a) The compounds of the present invention of the formula(I-2-17) in which n is 1 or 2, i.e., the compounds of the presentinvention of the formula (I-2-17a)

[0702] (wherein, n-2-17a is an integer of 1˜2 and the other symbols arethe same meaning as hereinbefore described.)

[0703] may be prepared by reacting the said compounds of the formula(I-11-a) or the compounds of the formula (I-1-1b) and the compounds ofthe formula (IV)

[0704] (wherein all the symbols are the same meanings as hereinbeforedescribed.).

[0705] This reaction may be carried out by the same procedure describedin the reaction of the compounds of the formula (I-2-15a) and thecompounds of the formula (III) in [15].

[0706] (b) The compounds of the present invention of the formula(I-2-17) in which n is 0, i.e., the compounds of the formula (I-2-17b)

[0707] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by reduction of the compounds of the formula(V)

[0708] (wherein all the symbols are the same meanings as hereinbeforedescribed.).

[0709] This reduction is known one. For example, it may be carried outby hydrogenation or by the method using triethylsilane.

[0710] This hydrogenation is known reaction. For example, it may becarried out in inert solvent [ethers (e.g., tetrahydrofuran, dioxane,dimethoxy ethane, diethyl ether etc.), alcohols (e.g., methanol, ethanoletc.), benzenes (e.g., benzene, toluene etc.), ketones (e.g., acetone,methyl ethyl ketone etc.), nitrites (e.g., acetonitrile etc.), amides(e.g., dimethylformamide etc.), water, ethyl acetate, acetic acid ormixture of the said two or more solvents etc.], in the presence ofcatalyst to hydrogenate (e.g., Pd-C, palladium black, Pd, palladiumhydroxide, platinum oxide, Ni, Raney nickel, ruthenium chloride etc.),in the presence or absence of an inorganic acid (e.g., hydrochloricacid, sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboricacid etc.) or an organic acid (e.g., acetic acid, p-toluenesulfoniciacid, bromic acid, trifluoroacetic acid, formic acid etc.), at anordinary or increased pressure under an atmosphere of hydrogen gas, orin the presence of ammonium formate at 0˜200° C. When an acid is used,its salt may be used.

[0711] This reduction using triethylsilane is well known. For example,it may be carried out in trifluoroacetic acid, in the presence oftriethylsilane at 0˜100° C.

[0712] (c) The compounds of the present invention of the formula(I-2-17) in which n is 2, i.e., the compounds of the present inventionof the formula (I-2-17c)

[0713] (wherein all the symbols are the same meanings as hereinbeforedescribed.) may be prepared by oxidizing the compounds obtained by theabove mentioned method in which m is 0 and n is 2, i.e., the compoundsof the formula (I-2-15ac)

[0714] (wherein all the symbols are the same meanings as hereinbeforedescribed.).

[0715] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-1b) in [1].

[0716] The compounds of the present invention of the formula (I-2) maybe also prepared by not only the methods described in [15]˜[17] but alsothe following methods [18]˜[30].

[0717] [18] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substituted oxy or a groupcontaining substituted oxy, i.e., the compounds of the present inventionof the formula (I-2-18)

[0718] (wherein, R¹⁻²⁻¹⁸ and R²⁻²⁻¹⁸ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻¹⁸(s) and R²⁻²⁻¹⁸(s) is a substituted oxy or a groupcontaining substituted oxy and the other symbols are the same meaning ashereinbefore described.) may be prepared by the following methods(a)˜(b).

[0719] (a) The compounds of the present invention of the formula(I-2-18) may be prepared by eterification of the compounds of theformula (I-2) in which at least one of R¹(s) or R²(s) is hydroxy or agroup containing hydroxy, i.e., the compounds of the formula (I-2-18a)

[0720] (wherein, R^(1-2-18a) and R^(2-2-18a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-18a)(s) and R^(2-2-18a)(s) is a hydroxy or a groupcontaining hydroxy and the other symbols are the same meaning ashereinbefore described.)

[0721] and the corresponding compounds containing a group which isremoval (chloride, bromide, iodide, mesyl or tosyl etc.).

[0722] This eterification may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-2a) in [2].

[0723] (b) The compounds of the present invention of the formula(I-2-18) may be prepared by eterification of the compounds of theformula (I-2) in which at least one of R¹(s) is a hydroxy or a groupcontaining hydroxy, i.e., the compounds of the formula (I-2-18b)

[0724] (wherein, R^(1-2-18b) and R^(2-2-18b) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-18b)(s) and R^(2-2-18b)(s) is a hydroxy or a groupcontaining hydroxy and the other symbols are the same meaning ashereinbefore described.)

[0725] with corresponding compounds containing hydroxy.

[0726] This eterification may be carried out by the procedure forpreparation of the compounds of the formula (I-1-2b) in [2].

[0727] [19] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substituted amino or agroup containing substituted amino, i.e., the compounds of the presentinvention of the formula (I-2-19)

[0728] (wherein, R¹⁻²⁻¹⁹ and R²⁻²⁻¹⁹ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻¹⁹(s) and R²⁻²⁻¹⁹(s) is a substituted amino or a groupcontaining substituted amino and the other symbols are the same meaningas hereinbefore described.) may be prepared by the following methods(a)˜(d).

[0729] (a) The compounds of the present invention of the formula(I-2-19) may be prepared by reacting the compounds of the formula (I-2)in which at least one of R¹(s) or R²(s) is a halogen (chloride, bromide,iodide) or a group containing halogen, i.e., the compounds of theformula (I-2-19a)

[0730] (wherein, R^(1-2-19a) and R^(2-2-19a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-19a)(s) and R^(2-2-19a)(s) is a halogen (chloride,bromide, iodide) or a group containing halogen and the other symbols arethe same meaning as hereinbefore described.)

[0731] and the compounds containing amino.

[0732] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-3a) in [3].

[0733] (b) The compounds of the present invention of the formula(I-2-19) may be prepared by reacting the compounds of the formula (I-2)in which at least one of R¹(s) or R²(s) is an amino or a groupcontaining amino, i.e., the compounds of the formula (I-2-19b)

[0734] (wherein, R^(1-2-19b) and R^(2-2-19b) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-19b)(s) and R^(2-2-19b)(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containinghalogen (chloride, bromide, and iodide).

[0735] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-3a) in [3].

[0736] (c) The compounds of the present invention of the formula(I-2-19) may be prepared by reacting the compounds of the formula (I-2)in which at least one of R¹(s) or R²(s) is an amino or a groupcontaining amino, i.e., the compounds of the formula (I-2-19c)

[0737] (wherein, R^(1-2-19c) and R^(2-2-19c) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-19c)(s) and R^(2-2-19c)(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingcarbonyl.

[0738] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-3c) in (3].

[0739] (d) The compounds of the present invention of the formula(I-2-19) may be prepared by reductive amidation of the compounds of theformula (I-2) in which at least one of R¹(s) or R²(s) is a carbonyl or agroup containing carbonyl, i.e., the compounds of the formula (I-2-19d)

[0740] (wherein, R^(1-2-19d) and R^(2-2-19d) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R_(1-2-19d)(s) and R^(2-2-19d)(s) is a carbonyl or a groupcontaining carbonyl and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingamino.

[0741] This reductive amidation may be carried out by the same procedurefor preparation of the compounds of the formula (I-1-3c) in [3].

[0742] [20] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is an amide or a groupcontaining amide, i.e., the compounds of the present invention of theformula (I-2-20)

[0743] (wherein, R¹⁻²⁻²⁰ and R²⁻²⁻²⁰ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁰(s) and R²⁻²⁻²⁰(s) is an amide or a group containingamide and the other symbols are the same meaning as hereinbeforedescribed.) may be prepared by the following methods (a)˜(b).

[0744] (a) The compounds of the present invention of the formula(I-2-20) may be prepared by amidation of the compounds of the formula(I-2) in which at least one of at least one of R¹(s) or R²(s) is a —COOHor a group containing —COOH, i.e., the compounds of the formula(I-2-20a)

[0745] (wherein, R^(1-2-20a) and R^(2-2-20a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-1-20a)(s) and R^(2-2-20a)(s) is a —COOH or a groupcontaining —COOH and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingamino.

[0746] The amidation may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-4) in [4].

[0747] (b) The compounds of the present invention of the formula(I-2-20) may be prepared by amidation of the compounds of the formula(I-2) in which at least one of R¹(s) or R²(s) is an amino or a groupcontaining amino, i.e., the compounds of the formula (I-2-20b)

[0748] (wherein, R^(1-2-20b) and R^(2-2-20b) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-20b)(s) and R^(2-2-20b)(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingcarboxy.

[0749] The amidation may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-4) in [4].

[0750] [21] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is an ester or a groupcontaining ester, i.e., the compounds of the present invention of theformula (I-2-21)

[0751] (wherein, R¹⁻²⁻²¹ and R²⁻²⁻¹ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²(s) and R²⁻²⁻²¹(s) is an ester or a group containingester and the other symbols are the same meaning as hereinbeforedescribed.) may be prepared by the following methods (a)˜(b).

[0752] (a) The compounds of the present invention of the formula(I-2-21) may be prepared by esterification of the compounds of theformula (I-2) in which at least one of R¹(s) or R²(s) is a —COOH or agroup containing —COOH, i.e., the compounds of the formula (I-2-21a)

[0753] (wherein, R^(1-2-21a) and R^(2-2-21a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-21a)(s) and R^(2-2-21a)(s) is a —COOH or a groupcontaining —COOH and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containinghydroxy.

[0754] This esterification may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-5) in [5].

[0755] (b) The compounds of the present invention of the formula(I-2-21) may be prepared by esterification of the compounds of theformula (I-2) in which R¹(s) or R²(s) is a hydroxy or a group containinghydroxy, i e., the compounds of the formula (I-2-21b)

[0756] (wherein, R¹⁻²⁻²¹ and R^(2-2-21b) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-21b)(s) and R^(2-2-21b)(s) is a hydroxy or a groupcontaining hydroxy and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingcarboxy.

[0757] This esterification may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-5) in [5].

[0758] [22] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a sulfonamide or a groupcontaining sulfonamide, i.e., the compounds of the present invention ofthe formula (I-2-22)

[0759] (wherein, R¹⁻²⁻²² and R²⁻²⁻²² are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²²(s) and R²⁻²⁻²²(s) is a sulfonamide or a groupcontaining sulfonamide and the other symbols are the same meaning ashereinbefore described.) may be prepared by the following methods(a)˜(b).

[0760] (a) The compounds of the present invention of the formula(I-2-22) may be prepared by sulfonamidation of the compounds of theformula (I-2) in which at least one of R¹(s) or R²(s) is a —SO₃H or agroup containing —SO₃H, i.e., the compounds of the formula (VI)

[0761] (wherein, R^(1-2-22a) and R^(2-2-22a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-22a)(s) and R^(2-2-22a)(s) is a —SO₃H or a groupcontaining —SO₃H and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingamino.

[0762] The sulfonamidation may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-6a) in [6].

[0763] (b) The compounds of the present invention of the formula(I-2-22) may be prepared by sulfonamidation of the compounds of theformula (I-2) in which at least one of R¹(s) or R²(s) is an amino or agroup containing amino, i.e., the compounds of the formula (I-2-22b)

[0764] (wherein, R^(1-2-22b) and R^(2-2-22b) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-22b)(s) and R^(2-2-22b)(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingsulfo.

[0765] The sulfonamidation may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-6a) in [6].

[0766] [23] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substitutedaminocarbonyloxy or a group containing a substituted aminocarbonyloxy,i.e., the compounds of the present invention of the formula (I-2-23)

[0767] (wherein, R¹⁻²⁻²³ and R²⁻²⁻²³ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²³(s) and R²⁻²⁻²³(s) is a substituted aminocarbonyloxyor a group containing a substituted aminocarbonyloxy and the othersymbols are the same meaning as hereinbefore described,) may be preparedby reacting the compounds of the formula (I-2) in which at least one ofR¹(s) or R²(s) is a hydroxy or a group containing hydroxy, i.e., thecompounds of the formula (I-2-23a)

[0768] (wherein, R^(1-2-23a) and R^(2-2-23a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-23a)(s) and R^(2-2-23a)(s) is a hydroxy or a groupcontaining hydroxy and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingisocyanate.

[0769] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-7) in [7].

[0770] [24] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substitutedaminocarbonylamino or a group containing a substitutedaminocarbonylamino, i.e., the compounds of the present invention of theformula (I-2-24)

[0771] (wherein, R¹⁻²⁻²⁴ and R²⁻²⁻²⁴ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁴(s) and R²⁻²⁻²⁴(s) is a substitutedaminocarbonylamino or a group containing a substitutedaminocarbonylamino and the other symbols are the same meaning ashereinbefore described.) may be prepared by reacting the compounds ofthe formula (I-2) in which at least one of R¹(s) or R²(s) is an amino ora group containing amino, i.e., the compounds of the formula (I-2-24a)

[0772] (wherein, R^(1-2-24a) and R^(2-2-24a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-24a)(s) and R^(2-2-24a)(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containingisocyanate.

[0773] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-7) in [7].

[0774] [25] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substitutedoxycarbonylamino or a group containing a substituted oxyocarbonylamino,i.e., the compounds of the present invention of the formula (I-2-25)

[0775] (wherein, R¹⁻²⁻²⁵ and R²⁻²⁻²⁵ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁵(s) and R²⁻²⁻²⁵ (s) is a substitutedoxycarbonylamino or a group containing a substituted oxyocarbonylaminoand the other symbols are the same meaning as hereinbefore described.)may be prepared by reacting the compounds of the formula (I-2) in whichat least one of R¹(s) or R²(s) is an amino or a group containing amino,i.e., the compounds of the formula (I-2-25a)

[0776] (wherein, R^(1-2-25a) and R^(1-2-25a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-25a)(s) and R^(2-2-25a)(s) is an amino or a groupcontaining amino and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containinghaloformic acid ester.

[0777] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-9) in [9].

[0778] [26] The compounds of the present invention of the formula (I-1)in which at least one of R¹(s) or R²(s) is a substituted oxycarbonyloxyor a group containing a substituted oxycarbonyloxy, i.e., the compoundsof the present invention of the formula (I-2-26)

[0779] (wherein, R¹⁻²⁻²⁶ and R²⁻²⁻²⁶ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁶(s) and R²⁻²⁻²⁶(s) is a substituted oxycarbonyloxyor a group containing a substituted oxycarbonyloxy and the other symbolsare the same meaning as hereinbefore described.) may be prepared byreacting the compounds of the formula (I-2) in which at least one ofR¹(s) or R²(s) is a hydroxy or a group containing hydroxy, i.e., thecompounds of the formula (I-2-26a)

[0780] (wherein, R^(1-2-26a) and R^(2-2-26a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-26a)(s) and R^(2-22-6a)(s) is a hydroxy or a groupcontaining hydroxy and the other symbols are the same meaning ashereinbefore described.) and the corresponding compounds containinghaloformic acid ester.

[0781] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-9) in [9].

[0782] [27] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substituted (hydroxy)methylor a group containing substituted (hydroxy)methyl, i.e., the compoundsof the present invention of the formula (I-2-27)

[0783] (wherein, R¹⁻²⁻²⁷ and R²⁻²⁻²⁷ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁷(s) and R²⁻²⁻²⁷(s) is a substituted (hydroxy)methylor a group containing a substituted (hydroxy)methyl and the othersymbols are the same meaning as hereinbefore described.) may be preparedby reacting the compounds of the formula (I-2) in which at least one ofR¹(s) or R²(s) is a formyl, i.e., the compounds of the formula (I-2-27a)

[0784] (wherein, R^(1-2-27a) and R^(2-2-27a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-27a)(s) and R^(2-2-27a)(s) is a formyl and the othersymbols are the same meaning as hereinbefore described.) and Grignard'sreagents or corresponding derivatives containing lithium.

[0785] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-11a) in (11].

[0786] [28] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a substituted carbonyl or agroup containing a substituted carbonyl, i.e., the compounds of thepresent invention of the formula (I-2-28)

[0787] (wherein, R¹⁻²⁻²⁸ and R²⁻²⁻²⁸ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁸(s) and R²⁻²⁻²⁸(s) is a substituted carbonyl or agroup containing a substituted carbonyl and the other symbols are thesame meaning as hereinbefore described.) may be prepared by oxidizingthe said compounds of the formula (I-2-27).

[0788] This reaction may be carried out by the same procedure forpreparation of the compounds of the formula (I-1-12) in [12].

[0789] [29] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is an amino or a groupcontaining amino, i.e., the compounds of the present invention of theformula (I-2-29)

[0790] (wherein, R¹⁻²⁻²⁹ and R²⁻²²⁻²⁹ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻²⁹(s) and R²⁻²⁻²⁹(s) is an amino or a group containingamino and the other symbols are the same meaning as hereinbeforedescribed.) may be prepared by reduce of nitro in the compounds of theformula (I-2) in which at least one of R¹(s) or R²(s) is a nitro or agroup containing nitro, i.e., the compounds of the formula (I-2-29a)

[0791] (wherein, R^(2-2-29a) and R^(2-2-29a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-29a)(s) and R^(2-2-29a)(s) is a nitro or a groupcontaining nitro and the other symbols are the same meaning ashereinbefore described.).

[0792] The reduction of nitro may be carried out by the same procedurefor preparation of the compounds of the formula (I-1-13) in [13].

[0793] [30] The compounds of the present invention of the formula (I-2)in which at least one of R¹(s) or R²(s) is a —COOH, hydroxy or amino ora group containing —COOH, hydroxy or amino, i.e., the compounds of thepresent invention of the formula (I-2-30)

[0794] (wherein, R¹⁻²⁻³⁰ and R²⁻²⁻³⁰ are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R¹⁻²⁻³⁰(s) and R²⁻²⁻³⁰(s) is a —COOH, hydroxy or amino or agroup containing —COOH, hydroxy or amino and the other symbols are thesame meaning as hereinbefore described.) may be prepared by removal ofprotecting group in the compounds of the formula (I-2) in which —COOH,hydroxy or amino which is protected by a protecting group or a groupcontaining —COOH, hydroxy or amino which is protected by a protectinggroup, i.e., the compounds of the formula (I-2-30a)

[0795] (wherein, R^(1-2-30a) and R^(2-2-30a) are the same meanings ashereinbefore described for R¹ and R², respectively, provided that atleast one of R^(1-2-30a)(s) and R^(2-2-30a)(s) is a protected —COOH(e.g., it is protected by methyl, ethyl, t-butyl and benzyl etc.),protected hydroxy (e.g., it is protected by methoxymethyl,tetrahydropyranyl, t-butyldimethylsilyl, acetyl, benzyl etc.) orprotected amino (e.g., it is protected by benzyloxycarbonyl,t-butoxycarbonyloxy, trifluoroacetyl etc.) or a group containing such agroup and the other symbols are the same meaning as hereinbeforedescribed.) by an alkaline hydrolysis, by removal of protecting group inan acidic condition, by removal of silyl or by removal of protectinggroup based on hydrogenelysis. An alkaline hydrolysis, by removal ofprotecting group in an acidic condition, by removal of silyl or byhydrogenolysis may be carried out by same procedure for preparation ofthe compounds of the formula (I-1-14) in [14].

[0796] Reaction for removal of protecting group in the present inventionmeans an ordinal one which is well known to the person in the art, forexample, alkaline hydrolysis, removal of protecting group in an acidiccondition and hydrogenolysis. The aimed compounds of the presentinvention may be prepared easily by choice of these reactions.

[0797] As well known to the person in the art, a protecting group ofcarboxy includes, for example, methyl, ethyl, t-butyl and benzyl. Inaddition, such a group includes the other protecting group which isremovable selectively and easily, for example, one described in T. W.Greene, Protective Groups in Organic Synthesis, Wiley, New York, 1991.

[0798] A protecting group of hydroxy includes, for example,methoxymethyl, tetrahydropyranyl, t-butyidimethylsilyl, acetyl, andbenzyl. In addition, such a group includes the other protecting groupwhich is removable selectively and easily, for example, one described inT. W. Greene, Protective Groups in Organic Synthesis, Wiley, New York,1991.

[0799] A protecting group of amino includes, for example,benzyloxycarbonyl, t-butoxycarbonyl, trifluoroacetyl. In addition, sucha group includes the other protecting group which is removableselectively and easily, for example, one described in T. W. Greene,Protective Groups in Organic Synthesis, Wiley, New York, 1991.

[0800] The compounds of the formula (V) are known per se or may beprepared according to the following Reaction Scheme or by known methodseasily.

[0801] In Reaction Scheme, X is halogen.

[0802] The compounds of the formulae (III), (IV), (VI), (VII) or (VIII)used as starting materials have been known per se or may be prepared byknown methods easily.

[0803] Further, the compounds of the formula (I-1-1 c) in which A isbenzene, R¹ is carboxy, p is 1 and R¹ is bonded at 4-position, i.e., thecompounds of the formula (XI) are important intermediates of thecompounds of the formula (I) of the present invention. The methods forpreparation of the compounds of the formula (XI) are shown in thementioned Reaction Scheme 5. Next, each step is explained in detail.

[0804] The reaction to synthesis of the compounds of the formula (XIII)from the compounds of the formula (XII) is well known. For example, itmay be carried out in an inert organic solvent (acetonitrile, benzene,toluene, xylene, methyhlene chloride, chloroform, dimethoxy ethane,tetrahydrofuran, tetrahydropyran, dioxane, diethyl ether, acetone etc.)or mixture thereof, in the presence of Lewis acid (Znl₂, ZnCl₂, aluminumchloride, TiCl₂, lithium hypochloric acid, lithium borotetrafluoride,lithium hexafluoride etc.) and cyanide derivatives(trimethylsilylcyanide, diethyl aluminum cyanide, or diethylcyanophosphonate etc.) at 0˜40°C.

[0805] The reaction to synthesis of the compounds of the formula (XIV)from the compounds of the formula (XIII) is well known. For example, itmay be carried out in an inert organic solvent (benzene, toluene, ethylacetate, dioxane, dimethoxy ethane, diethyl ether, tetrahydrofuran,tetrahydropyran, the mixture thereof etc.) in the presence of oxidant(2,3-dichloro-5,6-dicyano-1,4-benzoquinon, chloranil(2,3,5,6-tetrachloro-1,4-benzoquinon) etc.) at room temperature torefluxing temperature. Or it may be carried out, for example, in anorganic solvent (ethylene glycol, oleic acid, diethylene glycol,dimethyl ether, toluene, benzene, xylene etc.) in the presence ofhydrogen acceptor (nitrobenzene, maleic acid, cyclohexen, oleic acid,1,5-cycloctadien, phenylacetylene, 2-butylic acid etc.) and in thepresence of metal catalyst (Pd—C, palladium hydroxide, palladium black,Pd, platinum oxide, Ni, Raney nickel, ruthenium chloride etc.) at 60°C.˜refluxing temperature.

[0806] The reaction to synthesis of the compounds of the formula (XI)from the compounds of the formula (XIV) is well known. For example, itmay be carried out in alcohol solvent (ethylene glycol, t-butanol,benzyl alcohol, methanol ethanol , propanol, isopropanol etc.) in thepresence of alkali (sodium hydroxide, potassium hydroxide, lithiumhydroxide etc.) at 60° C.˜refluxing temperature.

[0807] In each reaction in the present specification, obtained productsmay be purified by conventional techniques. For example, purificationmay be carried out by distillation at atmospheric or reduced pressure,by high performance liquid chromatography, by thin layer chromatographyor by column chromatography using silica gel or magnesium silicate, bywashing or by recrystallization. Purification may be carried out aftereach reaction, or after a series of reactions.

[0808] In addition, the optical isomers of the compounds of the presentinvention of the formula (I) may be obtained by an ordinal opticalseparation (e.g., separation by gas chromatography or by highperformance liquid chromatography, separation by crystallization todiastermeric salt or clathrate compounds or separation by preferentialcrystallization etc.) or by ordinal method for preparation of racemiccompound.

[0809] [Pharmacological Activities]

[0810] According to the following experiments, it has been proved thatthe compounds of the present invention of the formula (I) possessinhibitory activities of producing IL-6 and/or IL-12.

[0811] (1) Assaying Inhibitory Activity on IL-6 production and cellulartoxicity

[0812] [Experimental Method]

[0813] 1.5×10⁴ of A549 cells (human lung epithelial cell line) weresuspended in dalbeco-modified eagle medium (DMEM) containing 0.5% fetusbovine serum (abbreviated as FBS) (100 μl) and incubated in 96well-microplate over day and night. The test compound dissolved invarious kinds of solvents at various concentrations (20 μl) and TumorNecrosis Factor-α (TNF-α (Genzyme Co, Cat. No. TNF-H)) dissolved in DMEMat the concentration of 12.5 ng/ml (80 μl) were added thereto. Afterincubation for 24 hours, the supernatant (200 μl) was recovered to assaythe quantity of IL-6 using Enzyme Linked Immuno Solvent Assay (ELISA)Method (R&D Systems Co., Cat. No. D6050), to calculate inhibitoryactivity of the test compound and determine 50 % inhibitoryconcentration (IC₅₀). To the cells from which the supernatant wasremoved, a solution of brom3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolinium (abbreviatedas MTT (Dojin Chemical Laboratory, Cat. No. 345-01821)) dissolved inDMEM containing 1 0% FBS at the concentration of 0.5mg/ml (100 μl) wasadded and incubated for 3 hours. After removing MTT solution, methanol(100 μl) was added thereto. After lyse the cells, the intensity ofabsorbance on 570 nm as a control of 690 nm was determined to assaycellular toxicity of the test compound. As a result, it has been provedthat the compounds of the present invention possess an inhibitoryactivity on IL-6 production with an IC₅₀ value of 20 μM or less. Forexample, free compound of the compound of

EXAMPLE 20(4) possessed an inhibitory activity on IL-6 production withan IC₅₀ value of 4.4 μM and showed no cellular toxicity at 10 μM.

[0814] (2) Assaying Inhibitory Activity on IL-12 Production and CellularToxicity

[0815] [Experimental Method]

[0816] 2.0×10⁵ of peripheral monocyte prepared from healthy human bloodby Ficole gravity centrifugation method (Pharmacia Biotech Co, Cat. No.17-1440-02) were suspended in RPMI1640 medium containing 10% FBS (170μl). The test compound dissolved in various kinds of solvents at thevarious concentrations (10 μl) and 6000 units/ml of Interferon-γ (IFN-γ(Serotec Co, Cat. No. PHP050)) (10 μl) dissolved in RPMI1640 mediumcontaining 10% FBS. After incubation for 24 hours in 96 well-microplate,lipopolysaccharide (6 μg/ml) dissolved in RPMI1640 medium containing 10%FBS (LPS (Difco Co., Cat. No. 3120-25-0)) (10 μl) was added thereto.After incubation for 20 hours, the supernatant (150 μl) was recovered toassay the quantity of IL-12 using ELISA Method (R&D Systems Co, Cat. No.D1200), calculate for inhibitory activity of the test compound anddetermine 50% inhibitory concentration (IC₅₀) (see J. Exp. Med., 183,147 (1996)). To the cells from which the supernatant (150 μl) wasremoved, a solution of MTT dissolved in RPMI1640 medium containing 10%FBS at 1 mg/ml (50 μl) was added and incubated for 3 hours. 2-Propanolcontaining 0.04N HCl (100 μl) was added thereto. After lyse the cells,the intensity of absorbance on 570 nm as a control of 690 nm wasdetermined to assay cellular toxicity of the test compound. As aresults, it has been proved that the compounds of the present inventionpossess an inhibitory activity on IL-12 production with an IC₅₀ value of10 μM or less. For example, hydrochloride of the compound of Example20(4) possessed an inhibitory activity on IL-12 production with an IC₅₀of 0.11 μM and showed no cellular toxicity at 1 μM.

[0817] [Toxicity]

[0818] The toxicity of the compounds of the present invention is verylow and therefore, it is confirmed that these compounds are safe for useas medicine.

[0819] [Application for Pharmaceuticals]

[0820] The compounds of the present invention possess an inhibitoryactivity of producing IL-6 and/or IL-12 in animal, especially human, sothey are useful for prevention and/or treatment of, for example, variousinflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia,osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma,Kaposi's sarcoma, rheumatoid arthritis, gammopathy, Castleman's disease,atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis,multiple sclerosis, colitis, graft versus host immune diseases,infectious diseases.

[0821] For the purpose above described, the compounds of the generalformula (I) of the present invention, non-toxic salts, acid additionsalts, or hydrates thereof may be normally administered systematicallyor locally, usually by oral or parenteral administration.

[0822] The doses to be administered are determined depending upon age,body weight, symptom, the desired therapeutic effect, the route ofadministration, and the duration of the treatment etc. In the humanadult, the doses per person per dose are generally between 1 mg and 1000mg, by oral administration, up to several times per day, and between 0.1mg and 100 mg, by parenteral administration (preferred into vein) up toseveral times per day, or continuous administration between 1 and 24hrs. per day into vein.

[0823] As mentioned above, the doses to be used depend upon variousconditions. Therefore, there are cases in which doses lower than orgreater than the ranges specified above may be used.

[0824] The compounds of the present invention may be administered asinner solid composition's or inner liquid compositions for oraladministration, or as injections, liniments or suppositories etc. forparenteral administration.

[0825] Inner solid compositions for oral administration includecompressed tablets, pills, capsules, dispersible powders, and granules.Capsules contain hard capsules and soft capsules.

[0826] In such inner solid compositions, one or more of the activecompound(s) is or are, admixed with at least one inert diluent (lactose,mannitol, glucose, microcrystalline cellulose, starch etc.), connectingagents (hydroxypropyl cellulose, polyvinylpyrrolidone, magnesiummetasilicate aluminate etc.), disintegrating agents (cellulose calciumglycolate etc.), lubricating agents (magnesium stearate), stabilizingagents, assisting agents for dissolving (glutamic acid, asparaginic acidetc.) etc. to prepare pharmaceuticals by known methods. Thepharmaceuticals may, if desired, be coated with material such as sugar,gelatin, hydroxypropyl cellulose or hydroxypropyl cellulose phthalateetc., or be coated with two or more films. And further, coating mayinclude containment within capsules of absorbable materials such asgelatin.

[0827] Inner liquid compositions for oral administration includepharmaceutically-acceptable water-agents, emulsions, syrups and elixirsetc. In such liquid compositions, one or more of the active compound(s)is or are comprised in inert diluent(s) commonly used in the art(purified water, ethanol or mixture thereof etc.). Besides inertdiluents, such compositions may also comprise adjuvants such as wettingagents, suspending agents, sweetening agents, flavouring agents,perfuming agents and preserving agents.

[0828] Injections for parenteral administration include solutions,suspensions and emulsions, and solid injections. Aqueous solutions orsuspensions include distilled water for injection and physiological saltsolution. Non-aqueous solutions or suspensions include propylene glycol,polyethylene glycol, plant oil such as olive oil, alcohol such asethanol, POLYSOLBATE80 (registered trade mark) etc. Such compositionsmay comprise additional diluents: e.g. preserving agents, wettingagents, emulsifying agents, dispersing agents, stabilizing agent,assisting agents such as assisting agents for dissolving (for example,glutamic acid, asparaginic acid). They may be sterilized for example, byfiltration through a bacteria-retaining filter, by incorporation ofsterilizing agents in the compositions or by irradiation. They may alsobe manufactured in the form of sterile solid compositions and which canbe dissolved in sterile water or some other sterile diluent forinjection immediately before use.

[0829] Other compositions for parenteral administration include liquidsfor external use, and endermic liniments, ointments, spray,suppositories and pessaries which comprise one or more of the activecompound(s) and may be prepared by known methods.

[0830] Spray compositions may comprise additional substances other thaninert diluents: e.g. stabilizing agents such as sodium hydrogen sulfate,stabilizing agents to give isotonicity, isotonic buffer such as sodiumchloride, sodium citrate, citric acid. For preparation of such spraycompositions, for example, the method described in the U.S. Pat. Nos.2,868,691 or 3,095,355 may be used.

BEST MODE FOR CARRYING OUT THE INVENTION

[0831] The following reference Examples and Examples are intended toillustrate, but do not limit the present invention.

[0832] The solvents in parenthesis show the developing or elutingsolvents and the ratios of the solvents used are by volume inchromatographic separations. The solvents in parentheses in NMR show thesolvents used for measurement.

EXAMPLE 1 3-Phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0833]

[0834] To asolution of benzothiophene-1,1-dioxide (1 g) intetrahydrofuran (10 ml) were added triethylamine (1.55 ml) andthiophenol (798 mg). The reaction mixture was stirred for 4 hours atroom temperature. To the reaction mixture was water added. The mixturewas extracted with ethyl acetate. The extract was washed by water, asaturated aqueous solution of sodium chloride successively, dried overanhydrous sodium sulfate, and concentrated. The residue was purifiedwith chromatography on silica gel (hexane:ethyl acetate=1:1). Theobtained compound was then recrystallized from ethanol to give the titlecompound (1.18 g) having the following physical data.

[0835] TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

[0836] NMR (CDCl₃): δ 7.85-7.18 (9H, m), 4.98 (1H, t, J=7 Hz), 3.80 (1H,dd, J=14, 7 Hz), 3.51 (1H, dd, J=14, 7 Hz).

EXAMPLES 1(1)˜1(18)

[0837] By the same procedure as described in Example 1 using acorresponding thiol instead of thiophenol, the following compounds ofthe present invention were obtained.

EXAMPLE 1 (1)3-(Thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0838]

[0839] TLC: Rf 0.53 (hexane:ethyl acetate=1:1);

[0840] NMR (CDCl₃):δ 7.81-7.66 (m, 3H), 7.58-7.51 (m, 1H), 7.42 (dd,J=5.4, 1.4 Hz, 1H), 7.14 (dd, J=3.6, 1.4 Hz, 1H), 7.00 (dd, J=5.4, 3.6Hz, 1H), 4.78 (t-like, J=6.9 Hz, 1H), 3.80 (dd, J=14.0, 7.2 Hz, 1H),3.51 (dd, J=14.0, 6.6 Hz, 1H).

EXAMPLE 1 (2)3-(4-Methylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0841]

[0842] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[0843] NMR (CDCl₃): δ 7.85-7.57 (m, 4H), 7.42 (d, J=8.0 Hz, 2H), 7.21(d, J=8.0 Hz, 2H), 4.80 (t-like, J=6.5 Hz, 1H), 3.85 (dd, J=14.0, 7.5Hz, 1H), 3.38 (dd, J=14.0, 6.0 Hz, 1H).

EXAMPLE 1 (3)3-(4-Methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0844]

[0845] TLC: Rf 0.38 (hexane:ethyl acetate=2:1);

[0846] NMR (CDC₃): δ 7.82-7.45 (4H, m), 7.36 (2H, d, J=7 Hz), 6.85 (2H,d, J=7 Hz), 4.83 (1 H, t, J=7 Hz), 3.83 (3H, s), 3.74 (1 H, dd, J=13, 7Hz), 3.46 (1 H, dd, J=13, 7 Hz).

EXAMPLE 1 (4)3-(4-Chlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0847]

[0848] TLC: Rf 0.37 (hexane ethyl acetate=2:1);

[0849] NMR (CDCl₃): δ 7.88-7.67 (m, 4H), 7.32 (d, J=8.0 Hz, 2H), 7.25(d, J=8.0 Hz, 2H), 4.83 (t-like, J=7.0 Hz, 1H), 3.83 (dd, J=14.5, 6.5Hz, 1H), 3.52 (dd, J=14.5, 7.8 Hz, 1H).

EXAMPLE 1 (5)3-(4-Fluorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0850]

[0851] TLC Rf 0.36 (hexane:ethyl acetate=2:1);

[0852] NMR (CDCl₃): δ 7.80-7.32 (m, 6H), 7.04 (t-like, J=8.8 Hz, 2H),4.90 (t-like, J=6.6 Hz, 1H), 3.78 (dd, J=13.6, 7.6 Hz, 1H), 3.50 (dd,J=13.6, 6.4 Hz, 1H).

EXAMPLE 1 (6)3-(4-Hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0853]

[0854] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[0855] NMR (CDCl₃): δ 3.45 (dd, J=15, 7.5Hz, 1H), 3.75 (dd, J15, 7.5Hz,1H), 4.80 (t, J=7.5 Hz, 1H), 5.60 (s, 1H), 6.75 (d, J=7.5 Hz, 2H), 7.30(d, J=7.5 Hz, 2H), 7.45-7.80 (m, 4H).

EXAMPLE 1 (7)3-(3-Hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0856]

[0857] TLC: Rf 0.36 (hexane:ethyl acetate=1:1);

[0858] NMR (CDCl₃): δ 3.50 (dd, J=15, 7.5 Hz, 1H), 3.85 (dd, J=15, 7.5Hz, 1H), 5.00 (t, J=7.5 Hz, 1H), 5.65 (s, 1H), 6.75-7.00 (m, 3H),7.10-7.30 (m, 1H), 7.50-7.80 (m, 4H).

EXAMPLE 1 (8)3-(2-Hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0859]

[0860] TLC: Rf 0.33 (hexane ethyl acetate=1:1);

[0861] NMR (CDCl₃): δ 3.45 (dd, J=12.5, 5.0 Hz, 1H), 3.70 (dd, J=12.5,7.5 Hz, 1H), 4.80 (dd, J=7.5, 5.0 Hz, 1H), 6.65 (s, 1H), 6.90 (t, J=7.5Hz, 1H), 7.00 (d, J=7.5 Hz, 1H), 7.30 -7.80 (m, 6H).

EXAMPLE 1 (9)3-(Pyridin-4-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0862]

[0863] TLC: Rf 0.45 (ethyl acetate)

[0864] NMR (CDCl₃): δ 3.58 (dd, J=13, 6 Hz, 1H), 4.00 (dd, J=13, 6 Hz,1H), 5.22 (t, J=6 Hz, 1H), 7.20 (m, 2H), 7.69 (m, 4H), 8.51 (m, 2H)

EXAMPLE 1 (10)3-(Pyrimidin-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0865]

[0866] TLC: Rf 0.55 (hexane:ethyl acetate=1:2);

[0867] NMR (CDCl₃): δ 3.71 (dd, J=14, 7 Hz, 1H), 4.24 (dd, J=14, 7 Hz,1H), 5.70 (t, J=7 Hz, 1H), 7.10 (t, J=5 Hz, 1H), 7.52-7.85 (m, 4H), 8.58(d, J=5 Hz, 2H).

EXAMPLE 1 (11)3-(Thiazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0868]

[0869] TLC: Rf 0.52 (hexane:ethyl acetate=1:1);

[0870] NMR (CDCl₃): δ 3.55 (dd, J=13.4 Hz, 1H), 3.81 (dd, J=13, 7 Hz,1H), 5.60 (dd, J=7, 4 Hz, 1H), 7.57-7.80 (m, 6H).

EXAMPLE 1 (12)3-(3-Methylfuran-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0871]

[0872] TLC: Rf 0.45 (hexane ethyl acetate=4:1);

[0873] NMR (CDCl₃): δ 2.27 (s, 3H), 3.39 (dd, J=14.0 Hz, 6.0 Hz, 1H),3.75 (dd, J=14.0 Hz, 6.0 Hz, 1H), 4.69 (t, J=6.0 Hz, 1H), 6.07 (d, J=2.0Hz, 1H), 7.25 (d, J=2.0 Hz, 1H), 7.48-7.77 (m, 4H).

EXAMPLE 1 (13)3-(3-Methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0874]

[0875] TLC: Rf 0.44 (hexane:ethyl acetate=1:1);

[0876] NMR (CDCl₃): δ 3.50 (dd, J=12.5, 7.5 Hz, 1H), 3.75 (s, 3H), 3.80(dd, J=12.5, 7.5 Hz, 1H), 5.00 (t, J=7.5 Hz, 1H), 6.85-7.05 (m, 3H),7.20-7.30 (m, 1H), 7.50-7.80 (m, 4H).

EXAMPLE 1 (14)3-(2-Methoxycarbonylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0877]

[0878] TLC: Rf 0.40 (hexane ethyl acetate=1:1);

[0879] NMR (CDCl₃): δ 3.60 (dd, J=15, 7.5 Hz, 1H), 3.90 (s, 3H), 3.95(dd, J=15, 7.5 Hz, 1H), 5.25 (t, J=7.5 Hz, 1H), 7.30-7.80 (m, 7H),7.95-8.05 (m, 1H).

EXAMPLE 1 (15) 3-Cyclohexylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0880]

[0881] TLC: Rf 0.32 (hexane:ethyl acetate=3:1);

[0882] NMR (CDCl₃): δ 1.26-2.10 (m, 10H), 2.80-2.93 (m, 1H), 3.52 (dd,J=13.4, 7.4 Hz, 1H), 3.92 (dd, J=13.4, 7.4 Hz, 1H), 4.68 (t, J=7.4 Hz,1H), 7.47-7.54 (m, 1H), 7.59-7.67 (m, 1H), 7.70-7.75 (m, 2H).

EXAMPLE 1 (16)3-(Naphthalen-1-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0883]

[0884] TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

[0885] NMR (CDCl₃): δ 3.51 (dd, J=13.6, 5.8 Hz, 1H), 3.64 (dd, J=13.6Hz, 7.3 Hz, 1H), 5.01 (t-like, J=6.4 Hz, 1H), 7.40-7.79 (m, 8H),7.90-7.94 (m, 2H), 8.52-8.56 (m, 1H).

EXAMPLE 1 (17)3-(2-Methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0886]

[0887] TLC: Rf 0.49 (hexane:ethyl acetate=1:1);

[0888] NMR (CDCl₃): δ 3.55 (dd, J=12.5, 7.5 Hz, 1H), 3.75 (dd, J=12.5,7.5 Hz, 1H), 3.90 (s, 3H), 5.10 (t, J=7.5 Hz, 1H), 6.90-7.00 (m, 2H),7.30-7.80 (m, 6H).

EXAMPLE 1 (18)3-(1-Methylimidazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0889]

[0890] TLC: Rf 0.50 (hexane:ethyl acetate=1:2); NMR (CDCl₃):5 3.54 (dd,J=14, 3 Hz, 1H), 3.65 (s, 3H), 4.04 (dd, J=14, 9 Hz, 1H), 6.58 (d, J=2.7Hz, 1H), 6.65 (d, J=2.7 Hz, 1H), 6.95 (dd, J=9,3 Hz, 1H), 7.56 (m, 1H),7.67 (m, 2H), 7.85 (m, 1H).

EXAMPLE 2 3-Phenylsulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0891]

[0892] To potassium peroxymonosulfate (“OXONE” (trade name) marketedfrom Aldrich Co., abbreviated as OXONE®; 2.14 g), water (10 ml) wasadded. To a solution of a compound prepared in Example 1 (0.961 g) inmethanol (50 ml), thus obtained aqueous solution of OXONE® (5.5 ml) wasadded at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes.To the reaction mixture, water was added. The mixture was extracted byethyl acetate. The extract was washed by water (twice) and a saturatedaqueous solution of sodium chloride, and dried over anhydrous sodiumsulfate and concentrated. The residue was recrystallized from ethanol togive the title compound (361 mg) having the following physical data.

[0893] TLC: Rf 0.13 (hexane:ethyl acetate=1:1);

[0894] NMR (CDCl₃): δ 7.85-7.45 (9H, m), 4.57 (1H, t, J=7 Hz), 3.98 (1H,dd, J=14, 7 Hz), 3.19 (1H, dd, J=14, 7 Hz).

EXAMPLES 2 (1)˜2 (2)

[0895] By the same procedure as described in Example 2 using thecompounds prepared in Example 1 (1) and Example 1 (14) instead of thecompound prepared in Example 1, the following compounds of the presentinvention were obtained.

EXAMPLE 2 (1) 3-(Thiophen-2-yl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0896]

[0897] TLC: Rf 0.01 (hexane:ethyl acetate=1:1);

[0898] NMR (CDCl₃): δ 7.95-7.50 (4.5H m), 7.50-7.25 (1.5H, m), 7.25-7.10(1H, m), 4.99 (0.5H, dd, J=8.4, 4 Hz), 4.81(0.5H, dd, J=8.4, 4 Hz), 4.02(0.5H, dd, J=14.2, 4.4 Hz), 3.72-3.40 (1.5H, m).

EXAMPLE 2 (2)3-(2-Methoxycarbonylphenyl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0899]

[0900] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[0901] NMR (CDCl₃): δ 2.90 (dd, J=12.5, 7.5 Hz, 1H), 4.00 (s, 3H),4.00(dd, J=12.5, 7.5 Hz, 1H), 5.05 (t, J=7.5 Hz, 1H), 7.55-7.90 (m, 5H),8.10-8.25 (m, 3H).

EXAMPLE 3 3-Phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0902]

[0903] To OXONE® (2.14 9), water (10 ml) was added. To a solution of thecompound prepared in Example 1 (0.961 g) in methanol (50 ml),was addedthus obtained aqueous solution of OXONE® at room temperature. Thereaction mixture was stirred for 2 hours at room temperature. To thereaction mixture, water was added. The mixture was extracted by ethylacetate. The extract was washed by water (twice) and a saturated aqueoussolution of sodium chloride successively, dried over anhydrous sodiumsulfate, and concentrated. The residue was recrystallized from ethanolto give the compound of the present invention (1.54 g) having thefollowing physical data.

[0904] TLC: Rf 0.45 (hexane:ethyl acetate=1:1);

[0905] NMR (CDCl₃): δ 3.65-3.85 (m, 2H), 5.10 (dd, J=10, 5.0 Hz, 1H),7.40-7.80 (m, 8H), 8.05 (d, J=10 Hz, 1H).

EXAMPLES 3 (1)˜3 (17)

[0906] By the same procedure as described in Example 3 using thecompounds prepared in Examples 1 (1)˜1 (17) instead of the compoundprepared in Example 1, or using 3-chloroperbenzoic acid instead ofOXONE® as an oxidant, the following compounds of the present inventionwere obtained.

EXAMPLE 3 (1)3-(Thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0907]

[0908] TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

[0909] NMR (CDCl₃): δ 8.08 (d, J=5.0 Hz, 1H), 7.82-7.66 (m, 5H), 7.20(dd, J=5.0, 3.8Hz, 1H), 5.82 (dd, J=9.4, 3.1 Hz, 1H), 4.07 (dd, J=15.4,9.4 Hz, 1H), 3.83 (dd, J=15.4, 3.1 Hz, 1H).

EXAMPLE 3 (2) 3-(4-Methylphenyl)sulfonyl-2,3-dihidro-1,1-dioxidebenzo[b]thiophene

[0910]

[0911] TLC. Rf 0.11 (hexane:ethyl acetate=2:1);

[0912] NMR (CDCl₃): δ 8.04 (1H, d, J=8 Hz), 7.82-7.58 (3H, m), 7.53 (2H,d, J=9 Hz), 7.28 (2H, d, J=9 Hz), 5.08 (1 H, dd, J=1H, 8 Hz), 3.86-3.55(2H, m), 2.42 (3H, s).

EXAMPLE 3 (3)3-(4-Methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0913]

[0914] TLC: Rf 0.23 (hexane:ethyl acetate=1:1);

[0915] NMR (CDCl₃): δ 8.04 (1H, d, J=8 Hz), 7.88-7.60 (3H, m), 7.54 (2H,d, J=7 Hz), 6.91 (2H, d, J=7 Hz), 5.06 (1 H, t, J=7 Hz), 3.85 (3H, s),3.80-3.60 (2H, m).

EXAMPLE 3 (4)3-(4-Chlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0916]

[0917] TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

[0918] NMR (CDCl₃): δ 8.02 (1H, d, J=8 Hz), 7.85-7.58 (3H, m), 7.58-7.32(4H, m), 5.09 (1 H, t, J=7 Hz), 3.90-3.65 (2H, m).

EXAMPLE 3 (5)3-(4-Fluorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0919]

[0920] TLC: Rf 0.41 (hexane:ethyl acetate=1:1)

[0921] NMR (CDCl₃): δ 8.03 (1H, d, J=8 Hz), 7.90-7.45 (5H, m), 7.20-7.00(2H, m), 5.08 (1H, t, J=7 Hz), 3.80-3.75 (2H, m).

EXAMPLE 3 (6)3-(4-Hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0922]

[0923] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[0924] NMR (CD₃OD+CDCl₃): δ 7.97 (1 H, d, J=7 Hz), 7.85-7.55 (3H, m),7.46 (2H, d, J=9 Hz), 6.84 (2H, d, J=9 Hz), 5.09 (1H, t, J=7 Hz),3.90-3.60 (2H, m).

EXAMPLE 3(7)3-(3-Hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0925]

[0926] TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

[0927] NMR (CDCl₃+DMSO-d₆): δ 9.83 (1H, brs), 7.90-7.78 (1 H, m),7.78-7.50 (3H, m), 7.42-7.08 (4H, m), 5.28-5.10 (1H, m), 3.90-3.58 (2H,m).

EXAMPLE 3 (8)3-(2-Hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0928]

[0929] TLC: Rf 0.15 (hexane:ethyl acetate=1:1);

[0930] NMR (CDCl₃+DMSO-d₆): δ 7.90-7.42 (6H, m), 7.13 (1H, d, J=8 Hz),6.98 (1H, t, J=7 Hz), 5.71 (1H, dd, J=9, 5 Hz), 3.86 (1H, dd, J=14, 5Hz), 3.65 (1H, dd, J=14, 9 Hz).

EXAMPLE 3 (9)3-(Pyridin-4-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0931]

[0932] TLC: Rf 0.25 (hexane:ethyl acetate=1:2);

[0933] NMR (DMSO-d₆): δ 3.87 (dd, J=15, 3 Hz, 1H), 4.03 (dd, J=15, 9Hz,1H), 5.94 (dd, J=9, 3 Hz, 1H), 7.70 (dd, J=4, 2 Hz, 2H), 7.81 (m, 4H),8.88 (dd, J=4, 2 Hz, 2H).

EXAMPLE 3 (10)3-(Pyrimidin-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0934]

[0935] TLC: Rf 0.15 (methylene chloride);

[0936] NMR (DMSO-d₆): δ 4.00 (dd, J=16, 4 Hz, 1H), 4.12 (dd, J=16, 9 Hz,1H), 6.17 (dd, J=9, 4 Hz, 1H), 7.78 (m, 3H), 7.90 (m, 2H), 9.09 (dd,J=5, 1 Hz, 2H).

EXAMPLE 3 (11)3-(Thiazol-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0937]

[0938] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[0939] NMR (CDCl₃): δ 3.87 (dd, J=15, 9 Hz, 1H), 4.20 (dd, J=15, 5 Hz,1H), 5.39 (dd, J=9, 5 Hz, 1H), 7.61-7.81 (m, 4H), 7.99-8.08 (m, 2H).

EXAMPLE 3 (12)3-(3-Methylfuran-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]furan

[0940]

[0941] TLC: Rf 0.50 (hexane:ethyl acetate=3:2);

[0942] NMR (CDCl₃): δ 2.39 (s, 3H), 3.78 (dd, J=15, 4 Hz, 1H), 3.88 (dd,J=15, 8 Hz, 1H), 5.00 (dd, J=8, 4 Hz, 1H), 5.98 (d, J=2 Hz, 1H), 7.18(d, J=2 Hz, 1H), 7.60-7.80 (m, 3H), 8.02 (m, 1H).

EXAMPLE 3 (13)3-(3-Methyoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0943]

[0944] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[0945] NMR (CDCl₃): δ 3.65-3.90 (m, 2H), 3.75 (s, 3H), 5.10 (dd, J=10,5.0Hz, 1H), 7.10-7.50 (m, 4H), 7.60-7.80 (m, 3H), 8.00 (d, J=7.5 Hz,1H).

EXAMPLE 3 (14)3-(2-Methoxycarbonylphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0946]

[0947] TLC: Rf 0.59 (methylene chloride:ethyl acetate=9:1);

[0948] NMR (CDCl3): δ 8.01-7.97 (m, 1H), 7.84-7.63 (m, 7H), 6.06 (dd,J=9.0, 4.5 Hz, 1H), 4.04 (s, 3H), 3.92 (dd, J=14.0, 4.5 Hz, 1H), 3.63(dd, J=14.0, 9.0 Hz, 1H).

EXAMPLE 3 (15)3-Cyclohexylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0949]

[0950] TLC: Rf 0.37 (hexane:ethyl acetate=1:1);

[0951] NMR (CDCl₃): δ 1.13-1.68 (m, 8H), 1.90-1.96 (m, 1H), 2.15-2.19(m, 1H), 3.07-3.23 (m, 1H), 3.87 (dd, J=14.5, 8.2 Hz, 1H), 3.95 (dd,J=14.5, 5.2 Hz, 1H), 4.96 (dd, J=8.2, 5.2 Hz, 1H), 7.63-7.83 (m, 3H),7.96-8.00 (m, 1H).

EXAMPLE 3 (16 )3-(Naphthalen-1-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0952]

[0953] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[0954] NMR (CDCl₃): δ 3.38 (dd, J=14.4, 8.8 Hz, 1H), 3.77 (dd, J=14.4,5.0 Hz, 1H), 5.31 (dd, J=8.8, 5.0 Hz, 1H), 7.60-7.81 (m, 7H), 8.00-8.05(m, 1H), 8.22-8.28 (m, 2H), 8.72-8.77 (m, 1H).

EXAMPLE 3 (17)3-(2-Methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0955]

[0956] TLC: Rf 0.20 (hexane:ethyl acetate=1:1);

[0957] NMR (CDCl₃+DMSO-d₆): δ 3.65 (dd, J=15, 10 Hz, 1H), 3.80 (dd,J=15, 5.0 Hz, 1H), 4.00 (s, 3H), 5.55 (dd, J=10, 5.0 Hz, 1H), 7.05-7.20(m, 2H), 7.60-7.95 (m, 6H).

EXAMPLE 43-(4-(2-(Piperidin-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0958]

[0959] To a solution of the compound prepared in Example 3 (6) (283 mg)in dimetyhylformamide (5 ml) were added N-chloroethylpiperidine (193 mg)and cesium carbonate (1.0 g). The reaction mixture was stirred at roomtemperature overnight. To the reaction mixture, water was added. Themixture was extracted by ethyl acetate. The extract was washed by water(three times), a saturated aqueous solution of sodium chloride, driedover anhydrous sodium sulfate, and concentrated. The residue waspurified with column chromatography on silica gel (hexane:ethylacetate=1:1) to give the compound of the present invention (186 mg)having the following physical data.

[0960] TLC: Rf 0.54 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[0961] NMR (CDCl₃):δ 8.03 (1H, d, J=7 Hz), 7.85-7.55 (3H, m), 7.53 (2H,d, J=9 Hz), 6.92 (2H, d, J=9 Hz), 5.05 (1H, t, J=7 Hz), 4.13 (2H, t, J=6Hz), 3.85-3.60 (2H, m), 2.76 (2H, t, J=6 Hz), 2.49 (4H, brt, J=6 Hz),1.68-1.45 (6H, m).

EXAMPLES 4 (1)˜4 (4)

[0962] By the same procedure as described in Example 4 by using thecompounds prepared in Examples 3 (6)˜3 (8) and corresponding halogenatedcompounds, the following compounds of the present invention wereobtained.

EXAMPLE 4 (1) 3-(4- (2-(pyrrolidin-1-yl)ethoxy)phenyl)sulfonyl)-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0963]

[0964] TLC: Rf 0.35 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[0965] NMR (CDCl₃): δ 8.03 (1H, d, J=7 Hz), 7.90-7.40 (5H, m), 6.93 (2H,d, J=7 Hz), 5.18-4.95 (1H, m), 4.14 (2H, t, J=6 Hz), 3.90-3.60 (2H, m),2.91 (2H, t, J=6 Hz), 2.75-2.40 (4H, m), 1.84-1.74 (4H, m).

EXAMPLE 4 (2) 3-(4-(2-(Morpholine-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0966]

[0967] TLC: Rf 0.44 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[0968] NMR (CDCl₃): δ 8.05 (1H, d, J=7 Hz), 7.85-7.40 (5H, m), 6.91 (2H,d, J=7 Hz), 5.06 (1H, t, J=7 Hz), 4.13 (2H, t, J=6 Hz), 3.95-3.50 (6H,m), 2.80 (2H, t, J=6 Hz), 2.70-2.40 (4H, m).

EXAMPLE 4 (3)3-(3-Benzyloxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0969]

[0970] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[0971] NMR (CDCl₃): δ 8.02 (1H, d, J=7 Hz), 7.85-7.52 (3H, m), 7.52-7.10(9H, m), 5.15-4.85 (3H, m), 3.80-3.45 (2H, m).

EXAMPLE 4 (4)3-(2-Benzyloxyohenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0972]

[0973] TLC: Rf 0.37 (hexane ethyl acetate=1:1);

[0974] NMR (CDCl₃): δ 7.93 (1H, dd, J=8, 2 Hz), 7.85-7.30 (10 H, m),7.25-7.08 (2H, m), 5.52 (1H, dd, J=9, 5 Hz), 5.28 (2H, s), 3.79 (1H, dd,J=14, 5 Hz), 3.48 (1H, dd, J=14, 9 Hz).

EXAMPLE 53-(4-(Pyridin-2-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0975]

[0976] By the same procedure as described in Example 4 using thecompound prepared in Example 1 (6) instead of the compound prepared inExample 3 (6), and using a corresponding halogenated compound instead ofN-chloroethylpiperidine, the compound of the present invention havingthe following physical data was obtained.

[0977] TLC: Rf 0.58 (ethyl acetate)

[0978] NMR (CDCl₃): δ 8.65-8.55 (1H, m), 7.80-7.20 (9H, m), 7.00-6.90(2H, m), 5.20 (2H, s), 4.85 (1H, t, J=7.5 Hz), 3.75 (1H, dd, J=12.5, 7.5Hz), 3.45 (1H, dd, J=12.5, 7.5 Hz).

EXAMPLES 5 (1)˜5 (9)

[0979] By the same procedure as described in Example 5 using thecompounds prepared in Examples 1 (6)˜1 (8), the following compounds ofthe present invention were obtained.

EXAMPLE 5 (1)3-(4-Pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0980]

[0981] TLC: Rf 0.42 (ethyl acetate);

[0982] NMR (CDCl₃): δ 8.70-8.60 (2H, m), 7.80-7.30 (8H, m), 7.00-6.90(2H, m), 5.05 (2H, s), 4.85 (1H, t, J=5 Hz), 3.75 (1H, dd, J=15, 5 Hz),3.45 (1H, dd, J=15, 5 Hz).

EXAMPLE 5 (2)3-(4-(Pyridin-4-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0983]

[0984] TLC: Rf 0.33 (ethyl acetate);

[0985] NMR (CDCl₃): δ 8.65-8.60 (2H, m), 7.80-7.30 (8H, m), 7.00-6.90(2H, m), 5.10 (2H, s), 4.85 (1H, t, J=5 Hz), 3.75 (1H, dd, J=15, 5 Hz),3.45 (1H; dd, J=15, 5 Hz)

EXAMPLE 5 (3)3-(4-(3-Hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0986]

[0987] TLC: Rf 0.14 (hexane:ethyl acetate=1:1);

[0988] NMR (CD₃OD): δ 1.90-2.10 (m, 2H), 3.30-3.50 (m, 1H), 3.50-4.00(m, 3H), 4.00-4.20 (m, 2H), 4.90-5.10 (m, 1H), 6.80-7.00 (m, 2H),7.30-7.50 (m, 2H), 7.50-7.80 (m, 4H).

EXAMPLE 5(4)3-(3-(Pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo [b]thiophene

[0989]

[0990] TLC: Rf 0.44 (ethyl acetate);

[0991] NMR (CDCl₃): δ 3.50 (dd, J=12.5, 7.5 Hz, 1H), 3.80 (dd, J=12.5,7.5 Hz, 1H), 4.95-5.10 (m, 1H), 5.00 (s, 2H), 6.90-7.10 (m, 3H),7.20-7.40 (m, 2H), 7.50-7.80 (m, 5H), 8.50-8.70 (m, 2H).

EXAMPLE 5(5)3-(3-(3-Hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0992]

[0993] TLC: Rf 0.17 (hexane:ethyl acetate=1:1);

[0994] NMR (CDCl₃): δ 1.95-2.05 (m, 2H), 3.50 (dd, J=12.5, 7.5 Hz, 1H),3.80 (dd, J=12.5,7.5 Hz, 1H), 3.85 (t, J=7.5 Hz, 2H), 4.05 (t, J=7.5 Hz,2H), 5.00 (t, J=7.5 Hz, 1H), 6.80-7.05 (m, 3H), 7.20-7.30 (m, 1H),7.50-7.80 (m, 4H)).

EXAMPLES 5 (6)3-(2-(Pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0995]

[0996] TLC: Rf 0.16 (hexane:ethyl acetate=1:1);

[0997] NMR (CD₃OD): δ 3.50 (dd, J=15, 5.0 Hz, 1H), 3.85 (dd, J=15, 7.5Hz, 1H), 5.20 (dd, J=7.5, 5.0 Hz, 1H), 5.25 (s, 2H), 7.00 (t, J=7.5 Hz,1H), 7.20 (d, J=7.5 Hz, 1H), 7.35-7.70 (m, 7H), 8.00 (d, J=7.5 Hz, 1H),8.50 (dd, J=5.0, 2.5 Hz, 1H), 8.70 (d, J=2.5 Hz, 1H).

EXAMPLES 5 (7)3-(2-(3-Hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0998]

[0999] TLC: Rf 0.30 (hexane:ethyl acetate=1:2);

[1000] NMR (CDCl₃): δ 2.05-2.10 (m, 2H), 2.30-2.60 (m, 1H), 3.50 (dd,J=15, 5.0 Hz, 1H), 3.70 (dd, J=5, 7.5 Hz, 1H), 3.90 (t, J=5.0 Hz, 2H),4.20-4.40 (m, 2H), 5.10 (dd, J=7.5, 5.0 Hz, 1H), 6.90-7.00 (m, 2H), 7.30-7.80 (m, 6H).

EXAMPLE 5 (8)3-(4-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1001]

[1002] TLC: Rf 0.30 (toluene:ethyl acetate=4:1);

[1003] NMR (CDCl₃): δ 7.80-7.10 (6H, m), 6.80 (2H, d, J=10 Hz),5.10-4.70 (2H, m), 4.00 (2H, t, J=5 Hz), 3.75 (1H, dd, J=15, 7.5 Hz),3.60-3.40 (3H, m), 1.45 (9H, s).

EXAMPLE 5 (9)3-(3-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1004]

[1005] TLC: Rf 0.40 (hexane ethyl:acetate=1:1);

[1006] NMR (CDCl₃): δ 7.80-7.50 (4H, m), 7.40-7.20 (1H, m), 7.05-6.70(3H, m), 5.05-4.90 (2H, m), 3.95 (2H, t, J=5 Hz), 3.80 (1H, dd, J=15, 5Hz), 3.60-3.40 (3H, m), 1.45 (9H, s).

EXAMPLE 63-(4-(Pyridin-2-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1007]

[1008] By the same procedure as described in Example 3 using thecompound prepared in Example 5 instead of the compound prepared inExample 1, and then by converting into the corresponding hydrochlorideby a known method, the compound of the present invention having thefollowing physical data was obtained.

[1009] Free Compound:

[1010] TLC: Rf 0.44 (ethyl acetate);

[1011] NMR (DMSO-d₆): δ 8.60-8.55 (1H, m), 7.90-7.60 (7H, m), 7.50 (1H,d, J=7.5 Hz), 7.40-7.30 (1H, m), 7.20 (2H, d, J=7.5 Hz), 5.70 (1H, dd,J=10, 2.5 Hz), 5.30 (2H, s), 4.00 (1H, dd, J=15, 10 Hz), 3.75 (1H, dd,J=15, 2.5 Hz).

[1012] Hydrochloride:

[1013] TLC: Rf 0.49 (ethyl acetate:triethylamine=19:1);

[1014] NMR (CD₃OD): δ 3.80 (dd, J=15, 25 Hz, 1H), 3.95 (dd J-15, 10 Hz,1H), 5.50 (dd, J=10, 2.5 Hz, 1H), 5.60 (s, 2H), 7.20 (d, J=7.5 Hz, 2H),7.55-8 00 (m, 4H), 7.70 (d, J=7.5 Hz, 2H), 8.05-8.25 (m, 2H), 8.60-8.95(m, 2H).

EXAMPLES 6 (1)˜6 (9)

[1015] Using the compounds prepared in Examples 5 (1)˜5 (9) instead ofthe compound prepared in Example 5, by the same procedure as describedin Example 5, or by the same reaction using 3-chloroperbenzoic acidinstead of OXONE® as an oxidant, and if necessary, by converting intocorresponding salts, the following compounds of the present inventionwere obtained.

EXAMPLE 6 (1)3-(4-(Pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1016]

[1017] Free Compound:

[1018] TLC: Rf 0.27 (ethyl acetate);

[1019] NMR (CDCl₃): δ 8.70-8.55 (2H, m), 8.10-8.00 (1H, m), 7.80-7.50(6H, m), 7.40-7.30 (1H, m), 7.10-6.90 (2H, m), 5.15 (2H, s), 5.20-5.00(1H, m), 3.90-3.70 (2H, m).

[1020] Hydrochloride:

[1021] TLC: Rf 0.38 (ethyl acetate:triethylamine=19:1);

[1022] NMR (CD₃OD): δ 3.80 (dd,J=15,2.5 Hz, 1H), 3.95 (dd, J=15, 10 Hz,1H), 5.45 (s, 2H), 5.45-5.55 (m, 1H), 7.20 (d, J=10 Hz, 2H), 7.60-8.00(m, 4H), 7.60(d, J=10 Hz, 2H), 8.10-8.20 (m, 1H), 8.70-9.00 (m, 3H).

EXAMPLE 6 (2)3-(4-(Pyridin-4-ylmethyloxy)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1023]

[1024] Free Compound:

[1025] TLC: Rf 0.22 (ethyl acetate);

[1026] NMR (DMSO-d₆): δ 8.60 (2H, d, J=5 Hz), 7.90-7.65 (6H, m), 7.45(2H, d, J=5 Hz), 7.20 (2H, d, J=7.5 Hz), 5.75 (1 H, dd, J=7.5, 2.5 Hz),5.30 (2H, s), 4.00 (1 H, dd, J=15, 7.5 Hz), 3.80 (1 H, dd, J=15, 2.5Hz).

[1027] Hydrochloride:

[1028] TLC: Rf 0.35 (ethyl acetate:triethylamine=19:1);

[1029] NMR (DMSO-d₆): δ 3.80 (dd, J=15, 2.5 Hz, 1H), 4.00 (dd, J=15, 10Hz, 1H), 5.55 (s, 2H), 5.75 (dd, J=10, 2.5 Hz, 1H), 7.25 (d, J=10 Hz,2H), 7.65-7.90 (m, 4H), 7.70 (d, J=10 Hz, 2H), 7.95 (d, J=7.5 Hz, 2H),8.90 (d, J=7.5 Hz, 2H).

EXAMPLE 6 (3)3-(4-(3-Hydroxypropylpxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1030]

[1031] TLC: Rf 0.33 (ethyl acetate );

[1032] NMR (CDCl₃): δ 2.05 (quint., J=5.0 Hz, 2H), 3.70-3.90 (m, 2H),3.85 (t, J=5.0 Hz, 2H), 4.15 (t, J=5.0 Hz, 2H), 5.05 (t, J=7.5 Hz, 1H),6.90 (d, J=10 Hz, 2H), 7.50 (d, J=10 Hz, 2H), 7.60-7.80 (m, 3H), 8.05(d, J=7.5 Hz, 1H).

EXAMPLE 6 (4)3-(3-(Pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1033]

[1034] TLC: Rf 0.60 (ethyl acetate methanol:triethylamine=16:2:1);

[1035] NMR (CD₃OD): δ 3.85 (dd, J=15, 5.0 Hz, 1H), 3.95 (dd, J=15, 10Hz, 1H), 5.35 (d, J=12.5 Hz, 1H), 5.45 (d, J=12.5 Hz, 1H), 5.55 (dd,J=10, 5.0 Hz, 1H), 7.20-7.85 (m, 7H), 7.95 (d, J=7.5 Hz, 1H), 8.15 (dd,J=10, 7.5 Hz, 1H), 8.75 (d, J=7.5 Hz, 1H), 8.85 (d, J=5.0 Hz, 1H), 9.00(s, 1H).

EXAMPLE 6 (5) 3-(3-(3-Hydroxypropyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1036]

[1037] TLC: Rf 0.33 (ethyl acetate );

[1038] NMR (CDCl₃): δ 1.90-2.20 (m, 2H), 3.65-3.90 (m, 4H), 3.95-4.20(m, 2H), 5.10 (dd, J=10, 5.0 Hz, 1H), 7.10-7.30 (m, 3H), 7.30-7.45 (m,1H), 7.60-7.80 (m, 3H), 8.00 (d, J=5.0 Hz, 1H).

EXAMPLE 6 (6)3-(2-(Pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1039]

[1040] TLC: Rf 0.51 (ethyl acetate:methanol triethylamine=16:2:1);

[1041] NMR (DMSO-d₆): δ 3.70 (dd, J=15, 2.5 Hz, 1H), 3.95 (dd, J=15, 10Hz, 1H), 5.60 (s, 2H) 5.75 (dd, J=10, 2.5 Hz, 1H), 7.20-7.35 (m, 1H),7.40-7.60 (m, 2H), 7.60-7.90 (m, 5H), 7.95-8.10 (m, 1H), 8.60 (d, J=7.5Hz, 1H), 8.90 (d, J=5.0 Hz, 1H), 9.05 (s, 1H).

EXAMPLE 6 (7)3-(2-(3-Hydroxypropylpxy)phenyl)sulfonyl-2,3-dyhydro-1,1-dioxidebenzo[b]thiophene

[1042]

[1043] TLC: Rf 0.37 (ethyl acetate);

[1044] NMR (CDCl₃): δ 5 2.00-2.30 (m, 2H), 2.50-2.80 (m, 1H), 3.55 (dd,J=15, 10 Hz, 1H), 3.80 (dd, J=15, 5.0 Hz, 1H), 3.95 (t, J=5.0 Hz, 2H),4.25-4.50 (m, 2H), 5.65 (dd, J=10, 5.0 Hz, 1H), 7.10-7.20 (m, 2H),7.60-7.80 (m, 4H), 7.80-7.95 (m, 2H).

EXAMPLE 6 (8)3-(4-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1045]

[1046] TLC: Rf 0.40 (hexane ethyl:acetate=1:2);

[1047] NMR (DMSO-d₆): δ 1.40 (s, 9H), 3.80 (dd, J=15, 2.5 Hz, 1H),3.90-4.15 (m, 5H), 5.75 (dd, J=10, 2.5 Hz, 1H), 6.90-7.10 (m, 1H), 7.10(d, J=7.5 Hz, 2H), 7.60-7.85 (m, 4H), 7.65 (d, J=7.5 Hz, 2H).

EXAMPLE 6 (9)3-(3-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1048]

[1049] TLC: Rf 0.13 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 1.45 (s,9H), 3.45-3.55 (m, 2H), 3.70-4.00 (m, 4H), 4.85-5.00 (m, 1H), 5.10 (dd,J=10, 5.0 Hz, 1H), 7.00-7.50 (m, 4H), 7.60-7.80 (m, 3H), 8.05 (d, J=7.5Hz, 1H).

EXAMPLE 73-(4-(2-Aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1050]

[1051] To a solution of the compound prepared in Example 6 (8) (200 mg)in dioxane (25 ml) and methanol (5 ml), was added a solution of 4Nhydrochloric acid in dioxane (10 ml) at room temperature. The reactionmixture was stirred at room temperature for 30 minutes. The reactionmixture was concentrated to give the compound of the present invention(160 mg) having the following physical data.

[1052] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=16:3:1);

[1053] NMR (CD₃OD): δ 3.35 (t, J=5.0 Hz, 2H), 3.80 (dd, J=15, 5.0 Hz,1H), 3.95 (dd, J=15, 10 Hz, 1H), 4.30 (t, J=5.0 Hz, 2H), 5.45 (dd, J=10,5.0 Hz, 1H), 7.10 (d, J=7.5 Hz, 2H), 7.60 (d, J=7.5 Hz, 2H), 7.60-8.00(m, 4H).

EXAMPLE 7 (1) 3-(3-(2-Aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1054]

[1055] By the same procedure as described in Example 7 using thecompound prepared in Example 6 (9) instead of the compound prepared inExample 6 (8), the compound of the present invention having thefollowing physical data was obtained.

[1056] TLC: Rf 0.60 (ethyl acetate:methanol triethylamine=14:3:1);

[1057] NMR (CD₃OD): δ 3.25-3.45 (m, 2H), 3.80-4.00 (m, 2H), 4.15-4.35(m, 2H), 5.55 (dd, J=7.5, 2.5 Hz, 1H), 7.20-7.50 (m, 4H), 7.60-8.00 (m,4H).

EXAMPLE 83-(4-(2-(N,N-Dimethylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1058]

[1059] To a solution of the compound prepared in Example 7 (105 mg) and90% paraformaldehyde (87 mg) in a mixture of acetic acid (3 ml) andmethanol (3 ml), was added sodium cyanoborohydride (86 mg) at 0° C. Thereaction mixture was stirred at room temperature overnight. To thereaction mixture, a saturated aqueous solution of sodium bicarbonate wasadded. The mixture was extracted by ethyl acetate. The extract waswashed by water, dried over anhydrous magnesium sulfate, andconcentrated. The residue was purified with column chromatography onsilica gel (ethyl acetate:methanol:triethylamine=16:3:1). Then to asolution of the obtained compound in dioxane (25 ml) and methanol (5ml), was added a solution of 4N hydrochloric acid-dioxane (10 ml) atroom temperature. The reaction mixture was stirred for 30 minutes andconcentrated to give the compound of the present invention (35 mg)having the following physical data.

[1060] TLC: Rf 0.40 (ethyl acetate:methanol:triethylamine=16:3:1); NMR(CD₃OD): δ 3.10(s, 6H), 3.60 (t, J=5.0 Hz, 2H), 3.80 (dd, J=15, 2.5 Hz,1H), 3.95 (dd, J=15, 10 Hz, 1H), 4.45 (t, J=5.0 Hz, 2H), 5.50 (dd, J=10,2.5 Hz, 1H), 7.10 (d, J=7.5 Hz; 2H), 7-60 (d, J=7.5 Hz, 2H), 7.60-8.00(m, 4H).

EXAMPLE 8 (1)3-(3-(2-(N,N-Dimethylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1061]

[1062] By the same procedure as described in Example 8 using thecompound prepared in Example 7 (1) instead of the compound prepared inExample 7, the compound of the present invention having the followingphysical data was obtained.

[1063] TLC: Rf 0.44 (ethyl acetate:methanol:triethylamine=16:2:1);

[1064] NMR (DMSO-d₆): δ 2.80 (s, 6H), 3.50 (t, J=5.0 Hz, 2H), 3.85 (dd,J=15, 2.5 Hz, 1H), 4.00 (dd, J=15, 10 Hz, 1H), 4.30-4.55 (m, 2H), 5.90(dd, J=10, 2.5 Hz, 1H), 7.30-7.60 (m, 4H), 7.70-7.90 (m, 4H).

EXAMPLE 9 5-Nitro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1065]

[1066] By the same procedure as described in Example 1 using5-nitrobenzothiophene-1,1-dioxide instead of benzothiophene-1,1-dioxide,the compound of the present invention having the following physical datawas obtained.

[1067] TLC: Rf 0.35 (hexane:ethyl acetate=2:1);

[1068] NMR (CDCl₃): δ 8.52 (1 H, d, J=2 Hz), 8.38 (1 H, dd. J=8.4, 2.0Hz), 7.89 (1 H, d, J=8.4 Hz), 7.48-7.36 (5H, m), 4.97 (1H, dd, J=7.2,6.8 Hz), 3.92 (1H, dd, J=13.6, 7.2 Hz), 3.60 (1H, dd, J=13.6, 6.8 Hz).

EXAMPLES 9 (1)˜9 (17)

[1069] By the same procedure as described in Example 9 using acorresponding benzothiophene-1,1-dioxide instead of5-nitrobenzothiophene-1,1-dioxide, the following compounds wereobtained.

EXAMPLE 9 (1)

[1070] 6-Methoxy-3-phenylthio-2,3-dihydro-1,1-di oxidebenzo[b]thiophene

[1071] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[1072] NMR (CDCl₃): δ 3.52 (dd, J=13.6 Hz, 6.8 Hz, 1H), 3.81 (dd, J=13.6Hz, 6.8 Hz, 1H), 3.86 (s, 3H), 4.92 (t, J=6.8 Hz, 1H), 7.14-7.21 (m,2H), 7.32-7.40 (m, 3H), 7.40-7.43 (m, 2H), 7.57-7.61 (m, 1H).

EXAMPLE 9 (2) 4-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1073]

[1074] TLC: Rf 0.21 (hexane:methylene chloride=1:4);

[1075] NMR (CDCl₃): δ 3.60 (dd, J=14.0 Hz, 1.8 Hz, 1H), 3.71 (dd, J=14.0Hz, 6.9 Hz, 1H), 3.91 (s, 3H), 5.05 (dd, J=6.9 Hz, 1.8 Hz, 1H), 7.07(dd, J=8.1 Hz, 0.7 Hz, 1H), 7.29-7.37 (m, 4H), 7.48-7.56 (m, 3H).

EXAMPLE 9 (3)5-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1076]

[1077] TLC: Rf 0.62 (hexane:ethyl acetate=1:1);

[1078] NMR (CDCl₃): δ 3.51 (dd, 1H, J=14, 5 Hz), 3.79 (dd, 1H, J=14, 5Hz), 3.88 (s, 3H), 4.92 (t, 1H, J=5 Hz), 7.04 (dd, 1H, J=5 Hz, 2 Hz),7.13 (d, 1H, J=2 Hz), 7.35 (m, 3H), 7.44 (m, 2H), 7.63 (d, 1 H, J=5 Hz).

EXAMPLE 9 (4)7-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1079]

[1080] TLC: Rf 0.42 (hexane:ethyl acetate=1:1);

[1081] NMR (CDCl₃): δ 7.62-7.38 (1H, m), 7.58-7.28 (6H, m), 6.79 (1H, d,J=8.4 Hz), 4.89 (1H, t, J=7.6 Hz), 3.97 (3H, s), 3.78 (1H, dd, J=13.5,7.6 Hz), 3.52 (1H, dd, J=13.5, 7.6 Hz).

EXAMPLE 9 (5)4-Chloro-3-phenylthin-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1082]

[1083] TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

[1084] NMR (CDCl₃): δ 3.68 (dd, J=14.2, 3.0 Hz, 1H), 3.75 (dd, J=14.2,5.6 Hz, 1H), 5.00 (dd, J=5.6, 3.0 Hz, 1H), 7.35-7.40 (m, 3H), 7.49-7.59(m, 3H), 7.64-7.69 (m, 2H).

EXAMPLE 9 (6)5-(t-Butoxycarbonylamino)methyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1085]

[1086] TLC: Rf 0.44 (hexane:ethyl acetate=1:1);

[1087] NMR (CDCl₃): δ 1.45 (s, 9H), 3.60 (dd, J=12.5, 2.5 Hz, 1H), 3.75(dd, J=12.5 Hz, 7.5 Hz, 1H), 4.50 (dd, J=15, 5.0 Hz, 1H), 4.85 (dd,J=15, 7.5 Hz, 1H), 5.00-5.20 (m, 2H) 7.30-7.45 (m, 3H), 7.50-7.75 (m,5H).

EXAMPLE 9 (7)4,7-Dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1088]

[1089] TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

[1090] NMR (CDCl₃): δ 7.50-7.30 (5H, m), 7.20 (1H, d, J=7.8 Hz), 4.89(1H, dd, J=5.8, 2.2Hz), 3.75-3.55 (2H, m), 2.60 (3H, s), 2.54 (3H, s).

EXAMPLE 9 (8)4,6-Dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1091]

[1092] TLC: Rf 0.50 (hexane:ethyl acetate=2:1);

[1093] NMR (CDCl₃): δ 5 7.56-7.24 (7H, m), 4.90 (1H, dd, J=6.0, 1.8 Hz),3.80-3.66 (2H, m 2.56 (3H, s), 2.42 (3H, s).

EXAMPLE 9 (9)4-Ethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1094]

[1095] TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

[1096] NMR (CDCl₃): δ 5 7.65-7.30 (8H, m), 4.99 (1H, dd, J=5.9, 2.4 Hz),3.75-3.57 (2H, m 2.98 (2H, q, J=7.6 Hz), 1.37 (3H, t, J=7.6 Hz).

EXAMPLE 9 (10)4-Methoxy-5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1097]

[1098] TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

[1099] NMR (CDCl₃): δ 7.99 (1H, d, J=8.0 Hz), 7.60-7.50 (3H, m),7.45-7.35 (3H, m), 5.11 (1H, dd, J=5.9, 2.8 Hz), 4.45 (2H, q, J=7.0 Hz),4.09 (3H, s), 3.75-3.60 (2H, m), 1.44 (3H, t, J=7.0 Hz).

EXAMPLE 9 (11)4-Bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1100]

[1101] TLC: Rf 0.20 (hexane:ethyl acetate=3:1);

[1102] NMR (CDCl₃): δ 3.69 (dd, J=13.9, 2.8Hz, 1H), 3.74 (dd, J=13.9,5.3Hz, 1H), 4.94 (dd, J=5.3, 2.8 Hz, 1H), 7.37-7.39 (m, 3H), 7.45 (t,J=7.8 Hz, 1H), 7.57-7.60 (m, 2H), 7.71 (d, J=7.8 Hz, 1H), 7.84 (dd,J=7.8, 0.9 Hz, 1H).

EXAMPLE 9 (12)4-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1103]

[1104] TLC: Rf 0.21 (hexane:ethyl acetate=1:1);

[1105] NMR (CDCl₃): δ 3.49 (dd, J=13.9, 5.9 Hz, 1H), 3.81 (dd, J=13.9,7.5 Hz, 1H), 4.93 (dd, J=7.5, 5.9 Hz, 1H), 7.17 (dd, J=8.0, 0.5 Hz, 1H),7.25-7.51 (m, 7H).

EXAMPLE 9 (13)5-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1106]

[1107] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1108] NMR (CDCl₃): δ 3.51 (dd, J=14.0, 7.0 Hz, 1H), 3.78 (dd, J=14.0,7.0 Hz, 1H), 4.89 (t, J=7.0 Hz, 1H), 6.32 (s, 1H), 6.94 (dd, J=5.0 Hz,2.0 Hz, 1H), 7.12 (d, J=2.0 Hz, 1H), 7.35 (m, 3H), 7.43 (m, 2H), 7.58(d, J=5.0 Hz, 1H).

EXAMPLE 9 (14)6-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1109]

[1110] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1111] NMR (CDCl₃): δ 3.54 (dd, J=13.8, 5.9 Hz, 1H), 3.83 (dd, J=13.8,7.4 Hz, 1H), 4.91 (t-like, J=6.6 Hz, 1H), 7.10-7.15 (m, 2H), 7.31-7.42(m, 5H), 7.51-7.56 (m, 1H).

EXAMPLE 9 (15)7-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1112]

[1113] TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

[1114] NMR (CDCl₃): δ 7.50-7.20 (5H, m), 7.11 (1 H, d, J=8.0 Hz), 6.85(1 H, d, J=8.0 Hz), 6.68 (1H, dd, J=32.6, 6.6 Hz), 4.91 (1H, t, J=7.5Hz), 3.79 (1H, dd, 14, 7.5 Hz), 3.50 (1H, dd, J=14, 7.5 Hz).

EXAMPLE 9 (16) 3-Phenylthio-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine

[1115]

[1116] TLC: Rf 0.50 (hexane: ethyl acetate=1:1);

[1117] NMR (CDCl₃): δ 3.49 (dd, J=14.0, 7.0 Hz, 1H), 3.85 (dd, J=14.0,8.0 Hz, 1H), 4.91 (dd, J=8.0, 7.0 Hz, 1H), 7.40 (m, 5H), 7.58 (dd,J=8.0, 5.0 Hz, 1H), 8.08 (m, 1H), 8.76 (m, 1H).

EXAMPLE 9 (17)4,7-dihydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1118]

[1119] TLC: Rf 0.33 (methylene chloride:ethyl acetate=1:1);

[1120] NMR (CDCl₃): δ 9.25 (2H, brs), 7.55-7.45 (2H, m), 7.40-7.30 (3H,m), 6.96 (1H, d, J=8.8 Hz), 6.85 (1H, d, J=8.8 Hz), 5.09 (1 H, dd,J=7.4, 1.6 Hz), 3.71 (1H, dd, 13.9, 7.4 Hz), 3.50 (1H, dd, J=13.9, 1.6Hz).

EXAMPLE 105-Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1121]

[1122] To a solution of the compound prepared in Example 9 (790 mg) inchloroform (45 ml) was added 3-chloroperbenzoic acid (70 % purity, 1.21g). The reaction mixture was stirred at room temperature for 2 hours. Tothe reaction mixture, water was added. The mixture was extracted byethyl acetate. The extract was washed by 2N aqueous solution of sodiumhydroxide, water, a saturated aqueous solution of sodium chloridesuccessively, dried over anhydrous magnesium sulfate and concentrated.The residue was purified with column chromatography on silica gel(hexane:ethyl acetate=3:2) to give the compound of the present invention(497 mg) having the following physical data.

[1123] TLC: Rf 0.39 (hexane:ethyl acetate=1:1);

[1124] NMR (CDCl₃): δ 3.98 (dd, J=15.5, 3.0 Hz, 1H), 4.19 (dd, J=15.5,9.3 Hz, 1H), 5.95 (dd, J=9.3, 3.0 Hz, 1H), 7.59-7.67 (m 2H), 7.78-7.84(m, 3H), 8.11 (d, J=8.6 Hz, 1H), 8.41 (d, J=2.0 Hz, 1H), 8.51 (dd,J=8.6, 2.0 Hz, 1H).

EXAMPLES 10 (1)˜10 (16)

[1125] Using the compounds prepared in Examples 9 (1)˜9 (16) instead ofthe compound prepared in Example 9, by the same procedure as describedin Example 10, or by the same reaction using 3-chloroperbenzoic acidinstead of OXONE@, the following compounds of the present invention wereobtained.

EXAMPLE 10 (1) 6-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1126]

[1127] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[1128] NMR (CDCl₃): δ 3.66-3.82 (m, 2H), 3.87 (s, 3H), 5.00 (dd, J=7.5,5.5 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 7.24 (dd, J=8.8, 2.4 Hz, 1H),7.46-7.54 (m, 2H), 7.63-7.71 (m, 3H), 7.86 (d, J=8.8 Hz, 1H).

EXAMPLE 10 (2) 4-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1129]

[1130] TLC: Rf 0.17 (hexane:ethyl acetate=1:1);

[1131] NMR (CDCl₃): δ 3.49 (s, 3H), 3.76 (dd, J=14.9, 9.2 Hz, 1H), 4.31(dd, J=14.9, 1.3 Hz, 1H), 5.23 (dd, J=9.2, 1.3 Hz, 1H), 6.90 (d, J=8.0Hz, 1H), 7.31 (d, J=7.8 Hz; 1H) 745-7.54 (m, 3H), 7.58-7.68 (m, 1H),7.72-7.77 (m, 2H).

EXAMPLE 10 (3) 5-Methoxy-3-phenylsulfonyl-2,3-dihydro-1, 1-dioxidebenzo[b]thiophene

[1132]

[1133] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1134] NMR (CDCl₃): δ 3.70(dd, J=12, 8 Hz, 1H), 3.77(dd, J=12, 4 Hz,1H), 3.94(s, 3H), 5.01 (dd, J=8, 4 Hz, 1H), 7.12(d, J=8 Hz, 1H), 7.44(s,1H), 7.53(m, 3H), 7.68(m, 3H).

EXAMPLE 10 (4)7-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1135]

[1136] TLC: Rf 0.40 (hexane:ethyl acetate=1:2);

[1137] NMR (DMSO-d₆): δ 7.80-7.55 (6H, m), 7.27 (1H, d, J=8.2 Hz), 7.15(1H, d, J=8.2 Hz), 5.73(1H, dd, J=9.5, 3.4 Hz), 3.91 (1H, dd, J=15, 9.5Hz), 3.87 (3H, s), 3.69 (1H, dd, J=15, 3.4 Hz).

EXAMPLE 10 (5)4-Chioro-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1138]

[1139] TLC: Rf 0.43 (methylene chloride:ethyl acetate=15:1);

[1140] NMR (CDCl₃): δ 3.79 (dd, J=15.0, 9.2 Hz, 1H), 4.24 (dd, J=15.0,1.0 Hz, 1H), 5.26 (dd, J=9.2, 1.0 Hz, 1H), 7.46-7.66 (m, 6H), 7.77-7.81(m, 2H).

EXAMPLE 10 (6)4-(t-Butoxycarbonylamino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1141]

[1142] TLC: Rf 0.26 (hexane:ethyl acetate=1:1);

[1143] NMR (CDCl₃): δ 1.45 (s, 9H), 3.75 (dd, J=15, 10 Hz, 1H), 3.85(dd, J=15, 2.5 Hz, 1H), 4.40 (dd, J=5, 5.0 Hz, 1H), 4.95 (dd, J=15, 7.5Hz, 1H), 5.35 (m, 2H), 7.45-7.90 (m, 8H).

EXAMPLE 10 (7)4,7-Dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1144]

[1145] TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

[1146] NMR (DMSO-d₆): δ 7.81-7.70 (3H, m), 7.70-7.55 (2H, m), 7.48 (1 H,d, J=7.8 Hz), 7.38 (1H, d, J=7.8 Hz), 5.73 (1H, t, J=5.2 Hz), 3.84 (2H,d-like, J=5.2 Hz), 2.40 (3H, s), 2.36 (3H, s).

EXAMPLE 10 (8)4,6-Dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1147]

[1148] TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

[1149] NMR (DMSO-d₆): δ 7.82-7.70 (3H, m), 7.70-7.55 (2H, m), 7.42 (2H,d, J=5.4 Hz), 5.73 (1 H, t, J=4.8 Hz), 3.86-3.80 (2H, m), 2.38 (6H, s).

EXAMPLE 10 (9)4-Ethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1150]

[1151] TLC: Rf 0.22 (hexane:ethyl acetate=2:1);

[1152] NMR (CDCl₃): δ 7.68-7.40 (8H, m), 5.22 (1H, d, J=9.2 Hz), 3.99(1H, d, J=15.2 Hz), 3.76 (1 H, dd, J=15.2, 9.2 Hz), 3.07 (2H, dd, J=7.6,2.2 Hz), 1.33 (3H, t, J=7.6 Hz).

EXAMPLE 10 (10)4-Methoxy-5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1153]

[1154] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[1155] NMR (CDCl₃): δ 7.91 (1H, d, J=8.0 Hz), 7.83-7.45 (5H, m), 7.41(1H, d, J=8.0 Hz), 5.28 (1H, d-like, J=8.0 Hz), 4.42 (2H, q, J=7.0 Hz),4.17 (1H, dd, J=15, 1.6 Hz), 3.86 (3H, s), 3.75 (1H, dd, J=15, 8.0 Hz),1.43 (3H, t, J=7.0 Hz).

EXAMPLE 10 (11)4-Bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1156]

[1157] TLC: Rf 0.35 (hexane:ethyl acetate=1:1);

[1158] NMR (CDCl₃): δ 3.79 (dd, J=15.0, 9.2 Hz, 1H), 4.23 (dd, J=15.0,1.1 Hz, 1H), 5.23 (d-like, J=8.8 Hz, 1H), 7.44-7.54 (m, 3H), 7.62-7.70(m, 2H), 7.78-7.83 (m, 3H).

EXAMPLE 10 (12)4-Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1159]

[1160] TLC: Rf 0.22 (hexane:ethyl acetate=1:2);

[1161] NMR (DMSO-d₆): δ 3.96 (dd, J=15.0, 8.4 Hz, 1H), 4.08 (dd, J=15.0,1.8 Hz, 1H), 5.51 (dd, J=8.4, 1.8 Hz, 1H), 7.00 (d-like, J=8.0 Hz, 1H),7.16 (d, J=7.0 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.56-7.63 (m, 2H),7.71-7.81 (m, 3H).

EXAMPLE 10 (13)5-Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1162]

[1163] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[1164] NMR (DMSO-d₆): δ 3.66 (dd, J=14, 4 Hz, 1H), 3.90 (dd, J=14, 9 Hz,1H), 5.71 (dd, J=9, 4 Hz, 1H), 7.07 (m, 2H), 7.55-7.82 (m, 6H), 10.80(brs, 1H).

EXAMPLE 10 (14)6-Hydroxy-3-phenylsulfonyl-2,3-dyhydro-1,1-dioxidebenzo[b]thiophene

[1165]

[1166] TLC: Rf 0.37 (hexane:ethyl acetate=1:2);

[1167] NMR (DMSO-d₆): δ 3.73 (dd, J=15.2, 3.2 Hz, 1H), 3.96 (dd, J=15.2,9.2 Hz, 1H), 5.60 (dd, J=9.2, 3.2 Hz, 1H), 6.94 (s-like, 1H), 7.16(d-like, J=8.4 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.57-7.64 (m, 2H),7.71-7.76 (m, 3H).

EXAMPLE 10 (15)7-Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1168]

[1169] TLC: Rf 0.31 (hexane:ethyl acetate 1:2);

[1170] NMR (DMSO-d₆): δ 7.80-7.45 (6H, m), 6.98 (2H, d, J=8.4 Hz), 5.66(1H, dd, J=9.6, 3.2 Hz), 3.85 (1H, dd, J=15, 9.6 Hz), 3.68-3.58 (1H, m).

EXAMPLE 10 (16)3-Phenylsulfonyl-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine

[1171]

[1172] TLC: Rf 0.20 (hexane:ethyl acetate=1:1);

[1173] NMR (CDCl₃): δ 3.65 (dd, J=15, 8 Hz, 1H), 3.74 (dd, J=15, 6 Hz,1H), 5.04 (dd, J=8, 6 Hz, 1H), 7.58 (m, 2H), 7.69 (m, 4H), 8.48 (m, 1H),8.86 (m, 1H).

EXAMPLE 115-Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1174]

[1175] Under an atmosphere of argon, to a solution of the compoundprepared in Example 10 (110 mg) in ethanol (7.5 ml) and ethyl acetate(7.5 ml), was added 5% palladium-carbon (20 mg). The reaction mixturewas stirred at room temperature for 2 hours under an atmosphere ofhydrogen. The reaction mixture was filtrated through celite (tradename). The filtrate was concentrated. The residue was purified withcolumn chromatography on silica gel (methylene chloride:ethylacetate=2:1) to give the compound of the present invention (94 mg)having the following physical data. Then, it was converted into acorresponding salt by a known method to give the compound of the presentinvention having the following physical data.

[1176] Free Compound:

[1177] TLC: Rf 0.29 (hexane:ethyl acetate=1:2);

[1178] NMR (CDCl₃): δ 3.61 (dd, J=14.6, 8.3 Hz, 1H), 3.70 (dd, J=14.6,5.6 Hz, 1H), 4.34 (brs, 2H), 4.94 (dd, J=8.3, 5.6 Hz, 1H), 6.79 (dd,J=8.0, 2.0 Hz, 1H), 7.21 (d, J=2.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H),7.49-7.55 (m, 2H), 7.63-7.74 (m, 3H).

[1179] Hydrochloride:

[1180] TLC: Rf 0.47 (methylene chloride:methanol=18:1);

[1181] NMR (DMSO-d₆): δ 3.53 (dd, J=14.9, 3.8 Hz, 1H), 3.75 (dd, J=14.9,9.4 Hz, 1H), 5.58 (dd, J=9.4, 3.8 Hz, 1H), 6.76 (dd, J=8.6, 2.1 Hz, 1H),6.90 (d, J=2.1 Hz, 1H), 7.31 (d, J=8.6 Hz, 1H), 7.57-7.65 (m, 2H),7.72-7.79 (m, 3H).

EXAMPLE 125-Acetylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1182]

[1183] To a solution of the compound prepared in Example 11 (91 mg) inpyridine (2 ml), was added acetic anhydride (1 ml). The reaction mixturewas stirred at room temperature for 2 hours. The reaction mixture wasconcentrated. The residue was purified with column chromatography onsilica gel (hexane:ethyl acetate=1:1) to give the compound of thepresent invention (86 mg) having the following physical data.

[1184] TLC: Rf 0.20 (hexane:ethyl acetate=1:2);

[1185] NMR (CDCl₃): δ 2.24 (s, 3H), 3.66 (dd, J=14.8, 8.3 Hz, 1H), 3.75(dd, J=14.8, 5.2 Hz, 1H), 5.04 (dd, J=8.3, 5.2 Hz, 1H), 7.49-7.59 (m,3H), 7.66-7.75 (m, 3H), 7.87-7.94 (m, 2H), 8.04 (s-like, 1H).

EXAMPLE 135-Aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1186]

[1187] By the same procedure as described in Example 7 using thecompound prepared in Example 10 (6) instead of the compound prepared inExample 6 (8), the compound of the present invention having thefollowing physical data was obtained.

[1188] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=16:2:1);

[1189] NMR (DMSO-d₆): δ 3.80-4.00 (m, 2H), 4.35 (d, J=15 Hz, 1H), 4.55(d, J=15 Hz, 1H), 6.30-6.40 (m, 1H), 7.60-7.70 (m, 2H), 7.75-7.95 (m,5H), 8.00-8.15 (m, 1H), 8.30-8.65 (m, 2H).

EXAMPLE 144-(N,N-dimethylamino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1190]

[1191] By the same procedure as described in Example 8 using thecompound prepared in Example 13 instead of the compound prepared inExample 7, the compound of the present invention having the followingphysical data was obtained.

[1192] TLC: Rf 0.50 (ethyl acetate:methanol:triethylamine=16:2:1);

[1193] NMR (DMSO-d6): δ 2.65 and 2.70 (both s, total 3H), 2.85 and 2.90(both s, total 3H), 3.80 (d, J=12.5 Hz, 1H), 4.05 (dd, J=12.5, 7.5 Hz,1H), 4.50-4.70 (m, 1H), 4.70-4.90 (m, 1H), 6.35 (d, J=7.5 Hz, 1H),7.60-8.00 (m, 7H), 8.20-8.35 (m, 1H), 10.85 (brs, 1H).

EXAMPLE 154-Methoxy-5-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1194]

[1195] To a suspension of lithium aluminum hydride (54 mg) intetrahydrofuran (10 ml), was added a solution of the compound preparedin Example 10 (10) (300 mg) in tetrahydrofuran (10 ml) at −78° C.dropwise. The reaction mixture was stirred at −78° C. for 1 hour. Thereaction mixture was poured into ice-water. The mixture was extracted byethyl acetate. The extract was washed by water, a saturated aqueoussolution of sodium chloride, successively, dried over anhydrous sodiumsulfate, and concentrated. The residue was purified with columnchromatography on silica gel (hexane:ethyl acetate=1:1) to give thecompound of the present invention (51 mg) having the following physicaldata.

[1196] TLC: Rf 0.27 (hexane:ethyl acetate=1:2);

[1197] NMR (CDCl₃): δ 3.80 (dd, J=15.2, 9.3 Hz, 1H), 4.05 (s, 3H), 4.14(dd, J=15.2, 1.4 Hz, 1H), 5.28 (dd, J=9.3, 1.4 Hz, 1H), 7.46-7.54 (m,3H), 7.63-7.78 (m, 3H), 8.05 (d, J=8.0 Hz, 1H), 10.33 (d, J=0.6 Hz, 1H).

EXAMPLE 164-Methoxy-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1198]

[1199] By the same procedure as described in Example 1 using2-thiophenthiol and 4-methoxybenzothiophen-1,1-diol, the compound of thepresent invention having the following physical data was obtained.

[1200] TLC: Rf 0.27 (methylene chloride:hexane=4:1);

[1201] NMR (CDCl₃): δ 3.66 (d, J=5.5, 5.4 Hz, 1H), 3.73 (dd, J=15.5, 4.2Hz, 1H), 3.95 (s, 3H), 4.88 (dd, J=5.4, 4.2 Hz, 1H), 7.01 (dd, J=5.4,3.6 Hz, 1H), 7.09 (d, J=8.0 Hz, 1H), 7.19 (dd, J=3.6, 1.2 Hz, 1H), 7.27(d, J=8.0 Hz, 1H), 7.44 (dd, J=5.4, 1.2 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H).

EXAMPLE 174-Methoxy-3-(thioiphen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1202]

[1203] By the same procedure using the compound prepared in Example 16instead of the compound prepared in Example 9, the compound of thepresent invention having the following physical data was obtained.

[1204] TLC: Rf 0.46 (methylene chloride:ethyl acetate=10:1);

[1205] NMR (CDCl₃): δ 3.73 (s, 3H), 3.79 (dd, J=15.0, 9.2 Hz, 1H), 4.23(dd, J=15.0, 1.2 Hz, 1H), 5.32 (dd, J=9.2, 1.2 Hz, 1H), 7.04 (d, J=8.0Hz, 1H), 7.11 (dd, J=4.9, 3.8 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.53 (dd,J=3.8, 1.4 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 7.73 (dd, J=4.9, 1.4 Hz,1H).

EXAMPLE 184-(4-Nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1206]

[1207] To a solution of a compound prepared in Example 9 (12) (1.0 g) indimethylformamide (30 ml), were added 4-nitrobenzylbromide (947 mg) andpotassium carbonate (1.0 g). The reaction mixture was stirred at roomtemperature overnight. To the reaction mixture, water was added. Themixture was extracted by ethyl acetate. The extract was washed by water(three times), a saturated aqueous solution of sodium chloride, driedover anhydrous sodium sulfate, and concentrated. The residue waspurified with column chromatography on silica gel (hexane:ethylacetate=1:1) to give the compound of the present invention (1.1 g)having the following physical data.

[1208] TLC: Rf 0.29 (hexane:ethyl acetate=1:1);

[1209] NMR (CDCl₃): δ 8.25 (2H, d, J=8.5 Hz), 7.71 (2H, d, J=8.5 Hz),7.60-7.20 (7H, m), 7.10 (1H, d, J=8 Hz), 5.32 (2H, s), 5.11 (1H, dd,J=7, 2 Hz), 3.85-3.55 (2H, m).

EXAMPLES 18 (1)˜18 (40)

[1210] By the sane procedure as described in Example 18 using compoundsprepared in Examples 9 (12)˜9 (15) or Example 9 (17) and a correspondinghalogenated compound, the following compounds of the present inventionwere obtained.

EXAMPLE 18 (1)4-(3-Phenyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1211]

[1212] TLC: Rf 0.27 (hexane ethyl acetate 2:1);

[1213] NMR (CDCl₃): δ 7.54-7.42 (3H, m), 7.32-7.19 (6H, m), 7.10 (1H, d,J=8.0 Hz), 6.95-6.84 (3H, m), 5.01 (1H, dd, J=6.6, 2.2 Hz), 4.31 (2H, t,J=6.0 Hz), 4.20 (2H, t, J=6.0 Hz), 3.69 (1H, dd, J=13.9, 6.6 Hz), 3.59(1H, dd, J=13.9, 2.2 Hz), 2.31 (2H, quint, J=6.0 Hz).

EXAMPLE 18 (2)4-Benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1214]

[1215] TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

[1216] NMR (CDCl₃): δ 7.54-7.26 (12H, m), 7.13 (1H, d, J=9.0 Hz), 5.22(2H, s), 5.03 (1H, dd, J=6.0, 2.6 Hz), 3.71 (1H, dd, J=13.8, 6.0 Hz),3.63 (1H, dd, J=13.8, 2.6 Hz).

EXAMPLE 18 (3)4-(3-Benzyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1217]

[1218] TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

[1219] NMR (CDCl₃): δ 2.13 (quint, J=6.0 Hz, 2H), 3.58 (dd, J=14.0, 2.4Hz, 1H), 3.67 (dd, J=14.0, 6.6 Hz, 1H), 3.69 (t, J=6.0 Hz, 2H), 4.22 (t,J=6.0 Hz, 2H), 4.44 (d, J=12.0 Hz, 1H), 4.52 (d, J=12.0 Hz, 1H), 4.92(dd, J=6.6, 2.4 Hz, 1H), 7.08 (d-like, J=7.4 Hz, 1H), 7.26 (s, 5H),7.30-7.35 (m, 4H), 7.43-7.54 (m, 3H).

EXAMPLE 18 (4) 4-(Pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1220]

[1221] TLC: Rf 0.46 (ethyl acetate);

[1222] NMR (CDCl₃): δ 3.62 (dd, J=14.0, 2.2Hz, 1H), 3.72 (dd, J=14.0,6.2Hz, 1H), 5.04 (dd, J=6.2, 2.2 Hz, 1H), 5.23 (s, 2H), 7.15 (dd, J=8.0,1.0 Hz, 1H), 7.26-7.45 (m, 7H), 7.54 (t, J=8.0 Hz, 1H), 7.85-7.92 (m,1H), 8.63 (dd, J=4.7, 2.0 Hz, 1H), 8.76 (dd, J=2.0, 0.6 Hz, 1H).

EXAMPLE 18 (5)4-(Quinolin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1223]

[1224] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[1225] NMR (CDCl₃): δ 8.18 (1H, d, J=8 Hz), 8.10 (1H, d, J=8 Hz),7.92-7.68 (3H, m), 7.68-7.40 (4H, m), 7.40-7.22 (4H, m), 7.16 (1H, d,J=8 Hz), 5.53 (2H, s), 5.18 (1H, dd, J=7, 2 Hz), 3.76 (1H, dd, J=14, 7Hz), 3.66 (1H, dd, J=14, 2 Hz).

EXAMPLE 18 (6)4-(Pyridin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1226]

[1227] TLC: Rf 0.33 (ethyl acetate);

[1228] NMR (CDCl₃): δ 8.62 (1H, d, J=5 Hz), 7.80-7.58 (2H, m), 7.58-7.38(3H, m), 7.38-7.18 (5H, m), 7.11 (1H, d, J=8 Hz), 5.35 (2H, s), 5.15(1H, dd, J=7, 2 Hz), 3.85-3.58 (2H, m).

EXAMPLE 18 (7)4-(Pyridin-4-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1229]

[1230] TLC: Rf 0.15 (ethyl acetate);

[1231] NMR (CDCl₃): δ 8.78-8.55 (2H, m), 7.65-7.18 (9H, m), 7.07 (1H, d,J=8 Hz), 5.23 (2H, s), 5.11 (1H, dd, J=7, 2 Hz), 3.82-3.53 (2H, m).

EXAMPLE 18 (8)4-(3-(Pyridin-3-yl)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1232]

[1233] TLC: Rf 0.18 (ethyl acetate);

[1234] NMR (CDCl₃): δ 8.48-8.35 (m, 2H), 7.67-7.33 (m, 9H), 6.95 (d,J=8.0 Hz, 1H), 5.01 (d-like, J=8.5 Hz, 1H), 4.15-3.86 (m, 4H), 2.81 (t,J=7.0 Hz, 2H), 2.21-2.01 (m, 2H).

EXAMPLE 18 (9)4-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1235]

[1236] TLC: Rf 0.24 (hexane:ethyl acetate=1:2);

[1237] NMR (CDCl₃): δ 2.06-2.17 (m, 2H), 3.57 (dd, J=14.0, 2.2 Hz, 1H),3.67 (dd, J=14.0, 6.6 Hz, 1H), 3.91 (br, 2H), 4.27 (t, J=5.8 Hz, 2H),5.05 (dd, J=6.6, 2.2 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H), 7.30-7.38 (m, 4H),7.49-7.56 (m, 3H).

EXAMPLE 18 (10)5-Pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1238]

[1239] TLC: Rf 0.70 (hexane:ethyl acetate=2:1);

[1240] NMR (CDCl₃): δ 0.95 (t, J=7.0 Hz, 3H), 1.38-1.47 (m, 4H), 1.82(quint, J=6.8 Hz, 2H), 3.51 (dd, J=15, 7 Hz, 1H), 3.79 (dd, J=15, 7 Hz,1H), 4.00 (t, J=6.8 Hz, 2H), 4.89 (t, J=7.0 Hz, 1H), 7.01 (dd, J=8, 2Hz, 1H), 7.12 (d, J=2 Hz, 1H), 7.36-7.38 (m, 3H), 7.41-7.43 (m, 2H),7.61 (d, J=8 Hz, 1H).

EXAMPLE 18 (11)5-(2-Phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1241]

[1242] TLC: Rf 0.75 (hexane:ethyl acetate=1:1);

[1243] NMR (CDCl₃): δ 7.65 (1H, d, J=8.5 Hz), 7.45-7.42 (2H, m),7.34-7.29 (5H, m), 7.21 (1H, d, J=2.2 Hz), 7.09 (1 H, dd, J=8.5, 2.2Hz), 7.00 (1 H, t, J=7.0 Hz), 6.95 (1 H, d, J=8.5 Hz), 4.93 (1H, t,J=7.0 Hz), 4.38 (4H, m), 3.78 (1H, dd, J=14.0, 7.0 Hz), 3.52 (1H, dd,J=14.0, 7.0 Hz).

EXAMPLE 18 (12)5-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1244]

[1245] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[1246] NMR (CDCl₃): δ 2.10 (quint, J=6.5 Hz, 2H), 3.60 (dd, J=14, 6.7Hz,1H), 3.82 (dd, J=14, 6.7 Hz, 1H), 3.89 (t, J=6.5 Hz, 2H), 4.20 (t, J=6.5Hz, 2H), 4.98 (t, J=6.7 Hz, 1H), 7.20 (dd, J=8.5, 2.2 Hz, 1H), 7.35-7.47(m, 6H), 7.61 (d, J=8.5 Hz, 1H).

EXAMPLE 18 (13) 5-(Pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1247]

[1248] TLC: Rf 0.40 (ethyl acetate);

[1249] NMR (CDCl₃): δ 3.51 (dd, J=9.0, 4.5 Hz, 1H), 3.79 (dd, J=9.0, 5.0Hz, 1H), 4.91 (t-like, J=4.7 Hz, 1H), 5.14 (s, 2H), 7.11 (dd, J=5.6, 1.6Hz, 1H), 7.21 (d, J=1.6 Hz, 1H), 7.33-7.42 (m, 6H), 7.65 (d, J=5.6 Hz,1H), 7.77 (dt, J=5.4, 1.3 Hz, 1H), 8.63 (dd, J=3.2, 1.3 Hz, 1H), 8.70(d, J=1.3 Hz, 1H).

EXAMPLE 18 (14)5-(3-(Pyridin-3-yl)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1250]

[1251] TLC: Rf 0.16 (ethyl acetate);

[1252] NMR (CDCl₃): δ 8.36-8.28 (m, 2H), 7.78-7.55 (m, 4H), 7.42-7.36(m, 5H), 7.01 (d, J=8.0 Hz, 1H), 5.11 (d-like, J=9.0 Hz, 1H), 4.12 (t,J=7.0 Hz, 2H), 3.88-3.64 (m, 2H), 3.05 (t, J=7.0 Hz, 2H), 2.35-2.26 (m,2H).

EXAMPLE 18 (15)6-(3-Phenyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1253]

[1254] TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

[1255] NMR (CDCl₃): δ 7.61-7.56 (1H, m), 7.43-7.25 (7H, m), 7.19-7.15(2H, m), 6.95-6.89 (3H, m), 4.91 (1H, t-like, J=6.6 Hz), 4.22 (2H, t,J=6.0 Hz), 4.15 (2H, t, J=6.0 Hz), 3.80 (1H, dd, J=13.8, 7.3 Hz), 3.51(1H, dd, J=13.8, 7.3 Hz), 2.28 (2H, quint, J=6.0 Hz).

EXAMPLE 18 (16) 6-Benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1256]

[1257] TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

[1258] NMR (CDCl₃): δ 7.63-7.58 (1 H, m), 7.45-7.31 (10H, m), 7.27-7.23(2H, m), 5.10 (2H, s), 4.92 (1H, t-like, J=6.7 Hz), 3.81 (1H, dd,J=13.7, 7.5 Hz), 3.52 (1H, dd, J=13.7, 6.1 Hz).

EXAMPLE 18 (17)6-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1259]

[1260] TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

[1261] NMR (CDCl₃): 7.60-7.55 (1H, m), 7.43-7.31 (5H, m), 7.19-7.12 (2H,m), 4.91 (1H, t, J=6.8 Hz), 3.99 (2H, t, J=6.6 Hz), 3.80 (1H, dd,J=13.8, 7.3 Hz), 3.51 (1H, dd, J=13.8, 6.2 Hz), 1.80 (2H, quint, J=7.0Hz), 1.50-1.30 (4H, m), 0.92 (3H, t, J=7.0 Hz).

EXAMPLE 18 (18)6-(2-(Morpholin-4-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1262]

[1263] TLC: Rf 0.41 (hexane:ethyl acetate: triethylamine=2:4:1);

[1264] NMR (CDCl₃): δ 7.60 (1H, d, J=8.4 Hz), 7.42-7.32 (5H, m),7.22-7.16 (2H, m), 4.92 (1H, t-like, J=6.8 Hz), 4.15 (2H, t, J=5.8 Hz),3.81 (1H, dd, J=13.8, 7.2 Hz), 3.73 (4H, t-like, J=4.6 Hz), 3.52 (1H,dd, J=13.8, 6.1 Hz), 2.82 (2H, t, J=5.8 Hz), 2.57 (4H, t-like, J=4.6Hz).

EXAMPLE 18 (19)6-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1265]

[1266] TLC: Rf 0.33 (hexane:ethyl acetate 1:2);

[1267] NMR (CDCl₃): δ 2.06 (quint, J=6.1 Hz, 2H), 3.51 (dd, J=13.6, 6.2Hz, 1H), 3.80 (dd, J=13.6, 7.4 Hz, 1H), 3.85 (t, J=6.1 Hz, 2H), 4.17 (t,J=6.1 Hz, 2H), 4.92 (t-like, J=6.8 Hz, 1H), 7.16-7.21 (m, 2H), 7.32-7.45(m, 5H), 7.57-7.61 (m, 1H).

EXAMPLE 18 (20)6-(Pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1268]

[1269] TLC: Rf 0.31 (methylene chloride: ethyl acetate=2:1);

[1270] NMR (CDCl₃): “ 3.53 (dd, J=13.6, 6.2 Hz, 1H), 3.82 (dd, J=13.6,7.2 Hz, 1H), 4.93 (t-like, J=6.6 Hz, 1H), 5.12 (s, 2H), 7.23-7.28 (m,2H), 7.33-7.46 (m, 6H), 7.61-7.65 (m, 1H), 7.75-7.79 (m, 1H), 8.63 (dd,J=5.0, 1.6 Hz, 1H), 8.70 (d, J=1.6 Hz, 1H).

EXAMPLE 18 (21)6-(3-Nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1271]

[1272] TLC: Rf 0.49 (hexane:ethyl acetate=1:1),

[1273] NMR (CDCl₃): δ 8.33 (1H, brs), 8.22 (1H, dd, J=8, 2 Hz), 7.76(1H, d, J=7.8 Hz), 7.70-7.48 (2H, m), 7.48-7.16 (7H, m), 5.21 (2H, s),4.93 (1H, t-like, J=6.8 Hz), 3.83 (1H, dd, J=13.6, 7.6 Hz), 3.54 (1H,dd, J=13.6, 6.2 Hz).

EXAMPLE 18 (22)6-(3-Bromopropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1274]

[1275] TLC: Rf 0.48 (hexane:ethyl acetate=3:1);

[1276] NMR (CDCl₃). δ 2.35 (quint, J=7.5 Hz, 2H), 3.55 (t, J=7.5 Hz,2H), 3.59 (dd, J=15, 7 Hz, 1H), 3.80 (dd, J=15, 7 Hz, 1H), 4.18 (t,J=7.5 Hz, 2H), 4.92 (t, J=7 Hz, 1H), 7.20 (dd, J=9, 2 Hz, 1H), 7.34-7.43(m, 6H), 7.60 (d, J=9 Hz, 1H).

EXAMPLE 18 (23)7-Pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1277]

[1278] TLC: Rf 0.80 (hexane:ethyl acetate=1:1);

[1279] NMR (CDCl₃): δ 5 7.54 (1H, t, J=7.8 Hz), 7.45-7.21 (6H, m), 6.91(1H, d, J=8.6 Hz), 4.88 (1H, t, J=7.6 Hz), 4.11 (2H, t, J=7.0 Hz), 3.77(1H, dd, J=13.6, 7.6 Hz), 3.50 (1H, dd, J=13.6, 7.6 Hz), 1.87 (2H,quint, J=7.0 Hz), 1.50-1.30 (4H, m), 0.92 (3H, t, J=7.2 Hz).

EXAMPLE 18 (24)7-(2-Phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1280]

[1281] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[1282] NMR (CDCl₃): δ 7.58 (1H, t, J=7.8 Hz), 7.45-7.25 (8H, m), 7.06(1H, d, J=8.4 Hz), 7.05-6.90 (3H, m), 4.89 (1 H, t, J=7.6 Hz), 4.58-4.45 (2H, m), 4.45-4.35 (2H, m), 3.78 (1 H, dd, J=13.6, 7.6 Hz), 3.52(1H, dd, J=13.6, 7.6 Hz).

EXAMPLE 18 (25)7-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1283]

[1284] TLC: Rf 0.25 (hexane:ethyl acetate=1:2);

[1285] NMR (CDCl₃): δ 7.60-6.60 (8H, m), 4.90 (1 H, t, J=6.8 Hz),4.36-4.26 (2H, m), 3.90 (2H, br) 3.79 (1H, d, J=13.8, 6.8 Hz), 3.52 (1H,dd, J=13.8, 6.8 Hz), 2.50-2.05 (2H, m).

EXAMPLE 18 (26) 7-(Pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1286]

[1287] TLC: Rf 0.12 (hexane:ethyl acetate=1:2);

[1288] NMR (CDCl₃): δ 8.66 (1H, d, J=2.2 Hz), 8.57 (1H, dd, J=4.8, 1.8Hz), 7.93 (1H, d, J=8.2 Hz), 7.56 (1H, t, J=8.2 Hz), 7.45-7.30 (4H, m),6.97 (1H, d, J=8.2 Hz), 5.30 (2H, s), 4.92 (1H, t, J=7.0 Hz), 3.82 (1H,dd, J=13.8, 7.8 Hz), 3.54 (1H, dd, J=13.8, 7.8 Hz).

EXAMPLE 18 (27)4-(t-Butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1289]

[1290] TLC: Rf 0.33 (hexane:ethyl acetate=2:1);

[1291] NMR (CDCl₃): δ 7.57-7.46 (3H, m), 7.37-7.32 (4H, m), 6.93 (1H,d-like, J=8.0 Hz), 5.16 (1H, dd, J=6.6, 2.0 Hz), 4.61 (2H, s), 3.72 (1H,dd, J=13.9, 6.6 Hz), 3.61 (1H, dd, J=13.9, 2.0 Hz), 1.49 (9H, s).

EXAMPLE 18 (28)5-(t-Butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1292]

[1293] TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

[1294] NMR (CDCl₃): δ 1.50 (s, 9H), 3.48 (dd, J=14, 6.7 Hz, 1H), 3.82(dd, J=14, 6.7 Hz, 1H), 4.66 (s, 2H), 4.95 (t, J=6.7 Hz, 1H), 7.18 (dd,J=9, 2.3 Hz, 1H) 7.40-7.53 (m, 6H), 7.62 (d, J=9 Hz, 1H).

EXAMPLE 18 (29)6-(t-Butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1295]

[1296] TLC: Rf 0.44 (hexane:ethyl acetate 2:1);

[1297] NMR (CDCl₃): δ 7.61 (1H, d, J=8.7 Hz), 7.44-7.32 (5H, m), 7.24(1H, dd, J=8.7, 2.6 Hz), 7.08 (1H, d, J=2.6 Hz), 4.91 (1H, t-like, J=6.7Hz), 4.56 (2H, s), 3.80 (1H, dd, J=13.7, 7.3 Hz), 3.51 (1H, dd, J=13.7,6.1 Hz), 1.49 (9H, s).

EXAMPLE 18 (30)7-(t-Butoxycatbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1298]

[1299] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[1300] NMR (CDCl₃): δ 7.54 (1H, t, J=7.6 Hz), 7.45-7.27 (6H, m), 6.80(1H, d, J=8.0 Hz), 4.90 (1H, t, J=7.6 Hz), 4.69 (2H, s), 3.79 (1H, dd,J=13.6, 7.6 Hz), 3.52 (1H, dd, J=13.6, 7.6 Hz), 1.46 (9H, s).

EXAMPLE 18 (31)4-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1301]

[1302] TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

[1303] NMR (CDCl₃): δ 1.35 (s, 9H), 3.46-3.66 (m, 2H), 3.62 (dd, J=14.2,2.2 Hz, 1H), 3.73 (dd, J=14.2, 6.8 Hz, 1H), 4.11-4.25 (m, 2H), 5.06 (dd,J=6.8, 2.2 Hz, 1H), 5.39 (br, 1H), 7.08 (d, J=7.6 Hz, 1H), 7.31-7.39 (m,4H), 7.44-7.57 (m, 3H).

EXAMPLE 18 (32)4-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1304]

[1305] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1306] NMR (CDCl₃): δ 1.38 (s, 9H), 2.00-2.11 (m, 2H), 3.33-3.44 (m,2H), 3.59 (dd, J=14.0, 2.2 Hz, 1H), 3.69 (dd, J=14.0, 6.6 Hz, 1H), 4.17(t, J=5.9 Hz, 2H), 4.90 (br, 1H), 5.08 (dd, J=6.6, 2.2 Hz, 1H), 7.08(dd, J=8.1, 0.7 Hz, 1H), 7.29-7.38 (m, 4H), 7.48-7.56 (m, 3H).

EXAMPLE 18 (33)5-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1307]

[1308] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[1309] NMR (CDCl₃): δ 1.46 (s, 9H), 3.52 (dd, J=15, 6 Hz, 1H), 3.56 (t,J=7.5 Hz, 2H), 3.80 (dd, J=15, 6 Hz, 1H), 4.10 (t, J=7.5 Hz, 2H), 4.88(t, J=6 Hz, 1H), 4.99 (br, 1H), 7.03 (dd, J=9, 2 Hz, 1H), 7.12 (d, J=2Hz, 1H), 7.35-7.47 (m, 5H), 7.64 (d, J=9 Hz, 1H).

EXAMPLE 18(34)6-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1310]

[1311] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[1312] NMR (CDCl₃): δ 5 1.44 (s, 9H), 2.01 (quint, J=6.2 Hz, 2H), 3.32(q, J=6.2 Hz, 2H), 3.51 (dd, J=13.6, 6.0 Hz, 1H), 3.80 (dd, J=13.6, 7.4Hz, 1H), 4.06 (t, J=6.2 Hz, 2H), 4.69 (br, 1H), 4.91 (t-like, J=6.8 Hz,1H), 7.14-7.21 (m, 2H), 7.32-7.45 (m, 5H), 7.59 (d, J=8.4 Hz, 1H).

EXAMPLE 18(35)6-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1313]

[1314] TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

[1315] NMR (CDCl₃): δ 1.46 (s, 9H), 3.51 (dd, J=13.8, 6.2 Hz, 1H), 3.55(q, J=5.2 Hz, 2H), 3.81 (dd, J=13.8, 7.4 Hz, 1H), 4.06 (t, J=5.2 Hz,2H), 4.92 (t-like, J=6.4 Hz, 1H), 4.96 (br, 1H), 7.13 (d, J=2.4 Hz, 1H),7.18 (dd, J=8.5, 2.4 Hz, 1H), 7.32-7.45 (m, 5H), 7.60 (d, J=8.5 Hz, 1H).

EXAMPLE 18(36)7-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1316]

[1317] TLC: Rf 0.60 (hexane ethyl acetate=1:2);

[1318] NMR (CDCl₃): “ 7.60-7.24 (7H, m), 6.94 (1H, d, J=8.4 Hz), 5.38(1H, bs), 4.90 (1H, t, J=7.4 Hz), 4.30-4.05 (2H, m), 3.79 (1H, dd,J=13.7, 7.4 Hz), 3.60-3.40 (3H, m), 1.42 (9H, s).

EXAMPLE 18(37)4-(N-(t-Butoxycarbonyl)piperidin-4-yl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1319]

[1320] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[1321] NMR (CDCl₃): δ 7.60-7.42 (3H, m), 7.42-7.25 (4H, m), 7.04 (1 H,d, J=8.2 Hz), 5.05 (1 H, dd, J=6.6, 2.2 Hz), 4.80-4.60 (1H, m),3.85-3.32 (6H, m), 2.15-1.65 (4H, m), 1.48 (9H, s).

EXAMPLE 18(38) 4,7-B is [(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1322]

[1323] TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

[1324] NMR (CDCl₃): δ 7.53-7.30 (5H, m), 7.20-6.85 (2H, m), 5.40 (2H,brs), 5.03-4.85 (1H, m), 4.25-4.00 (4H, m), 3.90-3.40 (6H, m), 1.43(18H, s).

EXAMPLE 18(39)4-(3-Nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1325]

[1326] TLC: Rf 0.29 (hexane:ethyl acetate=1:1);

[1327] NMR (CDCl₃): δ 8.44 (1H, s), 8.24 (1 H, d, J=8.4 Hz), 7.86 (1H,d, J=8.0 Hz), 7.65-7.20, (8H, m), 7.14 (1H, d, J=7.2 Hz), 5.31 (2H, s),5.13 (1H, dd, J=2.6 Hz, 6.6 Hz), 3.80-3.56 (2H, m).

EXAMPLE 18(40)4,7-Bis(pyridin-3-ylmethyloxy)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1328]

[1329] TLC: Rf 0.20 (ethyl acetate:methanol=10:1);

[1330] NMR (CDCl₃): δ 8.75-8.72 (1H, m), 8.70-8.50 (4H, m), 7.96-7.82(2H, m), 7.46-7.24 (6H, m), 7.05 (1H, d, J=9.0 Hz), 6.93 (1H, d, J=9.0Hz), 5.25 (2H, s), 5.15 (2H, s), 5.01-4.95 (1H, m), 3.81-3.59 (2H, m).

EXAMPLE 194-(3-Hydroxypropyl)oxy-3-phenylsulfynyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1331]

[1332] By the same procedure as described in Example 2 using thecompound prepared in Example 18 (9) instead of the compound prepared inExample 1, the compound of the present invention having the followingphysical data was obtained.

[1333] TLC: Rf 0.18 (hexane:ethyl acetate=1:1);

[1334] NMR (CDCl₃): δ 2.17 (quint, J=6.0 Hz, 2H), 3.08 (dd, J=14.0, 8.6Hz, 1H), 3.94 (t, J=6.0 Hz, 2H), 3.98 (dd, J=14.0, 4.8 Hz, 1H), 4.32 (t,J=6.0 Hz, 2H), 4.15 (dd, J=8.6, 4.8 Hz, 1H), 7.18 (d, J=7.9 Hz, 1H),7.35 (d, J=7.9 Hz, 1H), 7.55-7.66 (m, 6H).

EXAMPLE 204-(4-Nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1335]

[1336] By the same procedure as described in Example 10 using thecompound prepared in Example 18 instead of the compound prepared inExample 9, the compound of the present invention having the followingphysical data was obtained.

[1337] TLC: Rf 0.67 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1338] NMR (DMSO-d₆): δ 8.25 (2H, d, J=9 Hz), 7.78-7.52 (6H, m),7.52-7.20 (4H, m), 5.74 (1H, d, J=9 Hz), 5.26 (1H, d, J=14 Hz), 4.99(1H, d, J=14 Hz), 4.19 (1H, d, J=15 Hz), 4.00 (1H, dd, J=15, 9 Hz).

EXAMPLES 20 (1)˜20 (39)

[1339] Using the compounds prepared in Examples 18 (1)˜18 (39) insteadof the compound prepared in Example 18 by the same procedure asdescribed in Example 20, or by the same reaction using3-chloroperbenzoic acid instead of OXONEO as an oxidizer, and, ifnecessary, by converting into the corresponding salts by known methods,the following compounds of the present invention were obtained.

EXAMPLE 20 (1)4-(3-Phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1340]

[1341] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[1342] NMR (CDCl₃): δ 2.20 (quint, J=6.0 Hz, 2H), 3.70 (dd, J=14.8, 9.3Hz, 1H), 3.99-4.28 (m, 4H), 4.20 (dd, J=14.8, 1.2 Hz, 1H), 5.19 (dd,J=9.3, 1.2 Hz, 1H), 6.89-7.01 (m, 4H), 7.21-7.50 (m, 6H), 7.52-7.60 (m,1H), 7.65-7.70 (m, 2H).

EXAMPLE 20 (2)4-Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1343]

[1344] TLC: Rf 0.39 (hexane:ethyl=11);

[1345] NMR (CDCl₆): δ 3.73 (dd, J=15.0, 9.0 Hz, 1H), 4.22 (d, J=15.0 Hz,1H), 4.88 (d, J=11.7 Hz, 1H), 4.99 (d, J=11.7 Hz, 1H), 5.28 (d, J=9.0Hz, 1H), 7.04 (d, J=7.8 Hz, 1H), 7.26-7.40 (m, 8H), 7.49-7.58 (m, 2H),7.64-7.69 (m, 2H).

EXAMPLE 20 (3)4-(3-Benzyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1346]

[1347] TLC: Rf 0.26 (hexane:ethyl acetate=1:1);

[1348] NMR (CDCl₃): δ 1.96 (quint, J=6.1 Hz, 2H), 3.57-3.67 (m, 2H),3.67 (dd, J=14.9, 9.2 Hz, 1H), 3.82-3.92 (m, 1H), 3.98-4.09 (m, 1H),4.21 (dd, J=14.9, 0.5 Hz, 1H), 4.46 (d, J=12.1 Hz, 1H), 4.56 (d, J=12.1Hz, 1H). 5.05 (dd, J=9.2, 0.5 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H), 7.22-7.27(m, 6H), 7.35-7.60 (m, 4H), 7.65-7.69 (m, 2H).

EXAMPLE 20 (4)4-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1349]

[1350] free compound:

[1351] TLC: Rf 0.17 (ethyl acetate);

[1352] NMR (DMSO-d₆): δ 3.95 (dd, J=15.0, 8.8 Hz, 1H), 4.16 (dd, J=15.0,1.2 Hz, 1H), 4.93 (d, J=12.5 Hz, 1H), 5.15 (d, J=12.5 Hz, 1H), 5.66(d-like, J=8.0 Hz, 1H), 7.35-7.45 (m, 5H), 7.55-7.72 (m, 4H), 7.80 (dt,J=8.0, 1.4 Hz, 1H), 8.56 (dd, J=5.0, 1.4 Hz, 1H), 8.61 (d, J=1.4 Hz,1H).

[1353] Hydrochloride:

[1354] TLC: Rf 0.17 (ethyl acetate);

[1355] NMR (DMSO-d₆): δ 3.98 (dd, J=15.2, 8.6 Hz, 1H), 4.16 (d, J=15.2Hz, 1H), 5.10 (d, J=12.8 Hz, 1H), 5.29 (d, J=12.8 Hz, 1H), 5.85 (d,J=8.6 Hz, 1H), 7.38-7.59 (m, 5H), 7.66-7.75 (m, 3H), 7.94 (dd, J=8.0,5.4 Hz, 1H), 8.38 (d, J=8.0 Hz, 1H), 8.84 (d, J=5.4 Hz, 1H), 8.88 (s,1H).

[1356] Methanesulfonic Acid Salt:

[1357] TLC: Rf 0.31 (ethyl acetate:methanol=9:1);

[1358] NMR (DMSO-d₆): δ 2.37 (3H, s), 4.00 (dd, J=15.0, 8.8 Hz, 1H),4.17 (d-like, J=15.4 Hz, 1H), 5.13 (d, J=13.0 Hz, 1H), 5.32 (d, J=13.0Hz, 1H), 5.85 (d-like, J=8.0 Hz, 1H), 7.39-7.45 (m, 4H), 7.52-7.59 (m,1H), 7.66-7.77 (m, 3H), 8.05 (dd, J=8.2, 5.8 Hz, 1H), 8.49 (d, J=8.2 Hz,1H), 8.89-8.92 (m, 2H).

EXAMPLE 20 (5)4-(N-Oxidequinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1359]

[1360] TLC: Rf 0.38 (ethyl acetate:methanol: 28% ammoniawater=100:10:1);

[1361] NMR (CDCl₃): “ 8.77 (1H, d, J=8 Hz), 8.00-7.75 (4H, m), 7.75-7.63(3H, m), 7.63-7.45 (2H, m), 7.45-7.22 (3H, m), 7.17 (1H, d, J=8 Hz),5.72-5.25 (3H, m), 4.28 (1H, d, 15 Hz), 3.84 (1H, dd, J=15, 9 Hz).

EXAMPLE 20 (6a)4-(Pyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1362]

[1363] TLC: Rf 0.43 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1364] NMR (CDCl₃): “ 8.61 (1H, d, J=4 Hz), 7.88-7.18 (10H, m), 7.04(1H, d, J=8 Hz), 5.37 (1H, d, J=9 Hz), 5.11 (1 H, d, J=14 Hz), 4.98 (1H, d, J=14 Hz), 4.24 (1 H, d, J=15 Hz), 3.78 (1H, dd, J=15, 9 Hz).

EXAMPLE 20 (6b)4-(N-Oxidepyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1365]

[1366] TLC: Rf 0.09 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1367] NMR (CDCl₃+DMSO-d₆): δ 8.42-8.22 (1H, m), 7.90-7.20 (11H, m),5.83 (1H, d, J=8.5 Hz), 5.18 (1H, d, J=15 Hz), 4.93 (1H, d, J=15 Hz),4.21 (1H, d, J=15 Hz), 4.03 (1H, dd, J=15, 8.5 Hz).

EXAMPLE 20 (7) 4-(Pyridin-4-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1368]

[1369] Free Compound:

[1370] TLC: Rf 0.26 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1371] NMR (CDCl₃+DMSO-d₆): δ 8.57 (2H, d, J=6 Hz), 7.80-7.15 (10H, m),5.75 (1H, d, J=9 Hz), 5.15 (1H, d, J=14 Hz), 4.90 (1H, d, J=14 Hz), 4.19(1H, d, J=15 Hz), 4.00 (1H, dd, J=15, 9 Hz).

[1372] Hydrochloride:

[1373] TLC: Rf 0.31 (ethyl acetate:methanol=9:1);

[1374] NMR (DMSO-d₆): δ 8.93 (d, J=6.5 Hz, 2H), 8.00 (d, J=6.5 Hz, 2H),7.74-7.68 (m, 3H), 7.60-7.54 (m, 1H), 7.47-7.42 (m, 3H), 7.33 (d, J=8.0Hz, 1H), 5.93 (d, J=9.0 Hz, 1H), 5.46 (d, J=16.0 Hz, 1H), 5.18 (d,J=16.0 Hz, 1H), 4.19 (d, J=15.0 Hz, 1H), 4.03 (dd, J=15.0, 9.0 Hz, 1H).

[1375] Methanesulfonic Acid Salt:

[1376] TLC: Rf 0.31 (ethyl acetate:methanol=9:1);

[1377] NMR (DMSO-d₆): δ 8.94 (d, J=6.3 Hz, 2H), 8.03 (d, J=6.3 Hz, 2H),7.74-7.68 (m, 3H), 7.60-7.55 (m, 1H), 7.47-7.42 (m, 3H), 7.34 (d, J=8.0Hz, 1H), 5.92 (d, J=9.0 Hz, 1H), 5.46 (d, J=16.0 Hz, 1H), 5.19 (d,J=16.0 Hz, 1H), 4.19 (d, J=15.0 Hz, 1H), 4.03 (dd, J=15.0, 9.0 Hz, 1H),2.38 (s, 3H).

EXAMPLE 20 (8)4-(3-(Pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1378]

[1379] TLC: Rf 0.41 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1380] NMR (CDCl₃+CD₃OD): δ 8.50-8.36 (2H. m), 7.80-7.23 (9H, m), 7.00(1H, d, J=8 Hz), 5.27 (1H, d, J=9 Hz), 4.26-3.68 (4H, m), 2.88 (2H, t,J=7 Hz), 2.20-1.90 (2H, m).

EXAMPLE 20 (9)4-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1381]

[1382] TLC: Rf 0.26 (hexane:ethyl acetate=1:1);

[1383] NMR (CDCl₃): δ 2.02 (quint, J=5.6 Hz, 2H), 2.28 (t, J=5.6 Hz,1H), 3.71 (dd, J=14.8, 9.2 Hz, 1H), 3.91 (m, J=5.6 Hz, 2H), 4.05 (dd,J=14.8, 1.0 Hz, 1H), 4.10-4.17 (m, 2H), 5.28 (d-like, J=8.8 Hz, 1H),7.08 (d, J=8.4 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.42-7.62 (m, 4H),7.66-7.73 (m, 2H).

EXAMPLE 20 (10)5-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1384]

[1385] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[1386] NMR (CDCl₃): δ 0.96 (t, J=8 Hz, 3H), 1.42 (m, 4H), 1.86 (m, 2H),3.70 (dd, J=14, 8 Hz, 1H), 3.80 (dd, J=14,6 Hz, 1H), 4.07 (m, 2H), 5.00(dd, J=8,6 Hz, 1H), 7.10 (dd, J=8,2 Hz, 1H), 7.44 (d, J=2 Hz, 1H),7.46-7.77 (m, 6H).

EXAMPLE 20 (11)5-(2-Phenyloxyethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1387]

[1388] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[1389] NMR (CDCl₃): (3.70 (dd, J=14, 8 Hz, 1H), 3.77 (dd, J=14, 6 Hz,1H), 4.41 (m, 4H), 5.02 (dd, J=8, 6 Hz, 1H), 7.00 (m, 3H), 7.19 (dd,J=8, 2 Hz, 1H), 7.30-7.77 (m, 9H).

EXAMPLE 20 (12)5-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1390]

[1391] TLC: Rf 0.15 (hexane:ethyl acetate=1:1);

[1392] NMR (CDClo₃): δ 2.11 (m, 2H), 3.65 (dd, J=14, 8 Hz, 1H), 3.78(dd, J=14, 5 Hz, 1H), 3.89 (m, 2H), 4.25 (m, 2H), 5.01 (dd, J=8, 5 Hz,1H), 7.12 (dd, J=9, 2 Hz, 1H), 7.45-7.77 (m, 7H).

EXAMPLE 20 (13)5-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1393]

[1394] Free Compound:

[1395] TLC: Rf 0.30 (ethyl acetate);

[1396] NMR (DMSC-d₆): δ 3.79 (dd, J=15.1, 3.2 Hz, 1H), 4.00 (dd, J=15.1,9.4 Hz, 1H), 5.27 (s, 2H), 5.74 (dd, J=9.4, 3.2 Hz, 1H), 7.20 (d, J=2.2Hz, 1H), 7.36 (dd, J=8.7, 2.2 Hz, 1H), 7.47 (dd, J=7.8, 4.9 Hz, 1H),7.57-7.65 (m, 2H), 7.71-7.82 (m, 4H), 7.91 (dt, J=7.8, 2.0 Hz, 1H), 8.58(dd, J=4.9, 2.0 Hz, 1H), 8.71 (d, J=2.0 Hz, 1H).

[1397] Hydrochloride:

[1398] TLC: Rf 0.65 (ethyl acetate:triethylamine=10:1);

[1399] NMR (DMSO-d₆): δ 3.77 (dd, J=15.0, 3.4 Hz, 1H), 3.99 (dd, J=15.0,9.6 Hz, 1H), 5.43 (s, 2H), 5.77 (dd, J=9.6, 3.4 Hz, 1H), 7.30 (d, J=2.0Hz, 1H), 7.41 (dd, J=8.8, 2.2 Hz, 1H), 7.59-7.66 (m, 2H), 7.74-7.82 (m,4H), 8.02 (dd, J=8.4, 5.6 Hz, 1H), 8.57 (d-like, J=8.4 Hz, 1H), 8.88(d-like, J=5.6 Hz, 1H), 9.04 (s-like, 1H).

[1400] Methanesulfonic Acid Salt:

[1401] TLC: Rf 0.30 (ethyl acetate);

[1402] NMR (DMSO-d₆): δ 2.37 (3H, s), 3.77 (dd, J=15.0, 3.3 Hz, 1H),4.00 (dd, J=15.0, 9.3 Hz, 1H), 5.77 (dd, J=9.3, 3.3 Hz, 1H), 7.31 (d,J=2.2 Hz, 1H), 7.41 (dd, J=8.7, 2.2 Hz, 1H), 7.59-7.66 (m, 2H),7.74-7.83 (m, 4H), 8.06 (dd, J=8.0, 5.6 Hz, 1H), 8.61 (d-like, J=8.0 Hz,1H), 8.91 (dd, J=5.6, 1.0 Hz, 1H), 9.07 (d, J=1.6 Hz, 1H).

EXAMPLE 20 (14)5-(3-(Pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1403]

[1404] TLC: Rf 0.32 (ethyl acetate:methanol=10:1);

[1405] NMR (CD₃OD): δ 8.80 (1H, s), 8.71 (1H, d, J=6 Hz), 8.56 (1H, d,J=8 Hz), 8.02 (1H, t, J=7 Hz), 7.85-7.42 (6H, m), 7.27 (1H, d, J=10 Hz),7.14 (1H, s), 5.50-5.32 (1H, m), 4.16 (2H, t, J=6 Hz), 3.98-3.65 (2H,m), 3.10 (2H, t, J=7 Hz), 2.40-2.10 (2H, m).

EXAMPLE 20 (15)6-(3-Phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1406]

[1407] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[1408] NMR (CDCl₃): δ 2.29 (quint, J=6.0 Hz, 2H), 3.65-3.81 (m, 2H),4.15 (t, J=6.0 Hz, 2H), 4.21 (t, J=6.0 Hz, 2H), 4.99 (dd, J=7.3, 5.9 Hz,1H), 6.89-6.99 (m, 3H), 7.08 (d, J=2.2 Hz, 1H), 7.23 (dd, J=8.8, 2.2 Hz,1H), 7.25-7.33 (m, 2H), 7.45-7.52 (m, 2H), 7.62-7.70 (m, 3H), 7.85 (d,J=8.8 Hz, 1H).

EXAMPLE 20 (16)6-Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1409]

[1410] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1411] NMR (CDCl₃): δ 3.71 (dd, J=14.7, 7.7 Hz, 1H), 3.80 (dd, J=14.7,5.5 Hz, 1H), 5.00 (dd, J=7.7, 5.5 Hz, 1H), 5.10 (s, 2H), 7.15 (d, J=2.5Hz, 1H), 7.30 (dd, J=8.5, 2.5 Hz, 1H), 7.40-7.53 (m, 7H), 7.63-7.71 (m,3H), 7.87 (d, J=8.5 Hz, 1H).

EXAMPLE 20 (17)6-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1412]

[1413] TLC: Rf 0.26 (hexane:ethyl acetate 2:1);

[1414] NMR (CDCl₃): δ 0.94 (t, J=6.4 Hz, 3H), 1.42 (m, 4H), 1.81 (m,2H), 3.70 (dd, J=14.9, 7.6 Hz, 1H), 3.79 (dd, J=14.9, 5.7 Hz, 1H), 3.99(t, J=6.4 Hz, 2H), 5.00 (dd, J=7.6, 5.7 Hz, 1H), 7.04 (d, J=2.4 Hz, 1H),7.23 (dd, J=8.8, 2.4 Hz, 1H), 7.46-7.54 (m, 2H), 7.64-7.72 (m, 3H), 7.84(d, J=8.8 Hz, 1H).

EXAMPLE 20 (18)6-(2-(Morpholin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1415]

[1416] Free Compound:

[1417] TLC: Rf 0.27 (hexane:ethyl acetate: triethylamine=2:4:1);

[1418] NMR (CDCl₃): δ 2.56 (t, J=4.5 Hz, 4H), 2.81 (t, J=5.6 Hz, 2H),3.70-3.77 (m, 6H), 4.14 (t, J=5.6 Hz, 2H), 5.01 (dd, J=7.5, 5.7 Hz, 1H),7.08 (d, J=2.3 Hz, 1H), 7.25 (dd, J=8.7, 2.3 Hz, 1H), 7.47-7.54 (m, 2H),7.64-7.72 (m, 3H), 7.83 (d, J=8.7 Hz, 1H).

[1419] Hydrochloride:

[1420] TLC: Rf 0.27 (hexane ethyl acetate:triethylamine=4:8:1);

[1421] NMR (CD₃OD): δ 3.43-3.53 (m, 4H), 3.68 (t, J=4.8 Hz, 2H), 3.80(dd, J=15.4, 8.4 Hz, 1H), 3.95 (dd, J=15.4, 4.0 Hz, 1H), 3.92-4.02 (m,4H), 4.51 (t, J=4.8 Hz, 2H), 5.45 (dd, J=8.4, 4.0 Hz, 1H), 7.33 (d,J=2.6 Hz, 1H), 7.42 (dd, J=8.8, 2.6 Hz, 1H), 7.55-7.63 (m, 2H),7.71-7.81 (m, 4H).

EXAMPLE 20 (19)6-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1422]

[1423] TLC: Rf 0.22 (hexane:ethyl acetate=1:2);

[1424] NMR (CDCl₃): δ 2.06 (quint, J=6.0 Hz, 2H), 3.71 (dd, J=14.6, 7.5Hz, 1H), 3.79 (dd, J=14.6, 5.6 Hz, 1H), 3.85 (t, J=6.0 Hz, 2H), 4.16 (t,J=6.0 Hz, 2H), 5.00 (dd, J=7.5, 5.6 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),7.24 (dd, J=8.8, 2.4 Hz, 1H), 7.47-7.55 (m, 2H), 7.64-7.71 (m, 3H), 7.84(d, J=8.8 Hz, 1H).

EXAMPLE 20 (20)6-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1425]

[1426] Free Compound:

[1427] TLC: Rf 0.39 (ethyl acetate);

[1428] NMR (DMSO-d6): δ 3.78 (dd, J=15.2, 3.1 Hz, 1H), 4.01 (dd, J=15.2,9.2 Hz, 1H), 5.29 (s, 2H), 5.69 (dd, J=9.2, 3.1 Hz, 1H), 7.42-7.47 (m,3H), 7.58-7.66 (m, 3H), 7.74-7.82 (m, 3H), 7.89 (dt, J=8.0, 1.0 Hz, 1H),8.57 (dd, J=4.8, 1.6 Hz, 1H), 8.69 (d, J=1.6 Hz, 1H).

[1429] Hydrochloride:

[1430] TLC: Rf 0.39 (ethyl acetate);

[1431] NMR (DMSO-d₆): δ 3.78 (dd, J=15.2, 3.0 Hz, 1H), 4.01 (dd, J=15.2,9.4 Hz, 1H), 5.72 (dd, J=9.4, 3.0 Hz, 1H), 7.46-7.51 (m, 2H), 7.59-7.66(m, 3H), 7.75-7.83 (m, 3H), 7.99 (dd, J=8.0, 5.4 Hz, 1H), 8.52 (d, J=8.0Hz, 1H), 8.87 (dd, J=5.4, 1.2 Hz, 1H), 8.99 (d, J=1.2 Hz, 1H).

EXAMPLE 20 (21)6-(3-Nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1432]

[1433] TLC: Rf 0.55 (hexane:ethyl acetate=1:2);

[1434] NMR (DMSO-d₆): δ 8.36-8.34 (m, 1H), 8.25-8.20 (m, 1H), 7.93(d-like, J=7.6 Hz, 1H), 7.82-7.72 (m, 4H), 7.68-7.58 (m, 3H), 7.50-7.43(m, 2H), 5.70 (dd, J=9.4, 3.0 Hz, 1H), 5.40 (s, 2H), 4.02 (dd, J=15.2,9.4 Hz, 1H), 3.79 (dd, J=15.2, 3.0 Hz, 1H).

EXAMPLE 20 (22)6-(3-Bromopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1435]

[1436] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[1437] NMR (CDCl₃): δ 2.35 (m, 2H), 3.60 (t, J=6.0 Hz, 2H), 3.70-3.91(m, 2H), 4.17 (t, J=6.0 Hz, 2H), 5.01 (dd, J=14, 7 Hz, 1H), 7.09 (d,J=3.0 Hz, 1H), 7.25 (m, 1H), 7.53 (m, 2H), 7.67 (m, 3H), 7.89 (m, 1H).

EXAMPLE 20 (23)7-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1438]

[1439] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[1440] NMR (CDCl₃): δ 7.70-7.43 (7H, m), 6.99 (1H, d, J=8.2 Hz), 5.01(1H, dd, J=8.6, 5.4 Hz), 4.07 (2H, t, J=6.8 Hz), 3.73-3.68 (2H, m), 1.80(2H, quint., J=6.8 Hz), 1.50-1.20 (4H, m), 0.89 (3H, t, J=6.8 Hz).

EXAMPLE 20 (24)7-(2-Phenyloxyethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1441]

[1442] TLC: Rf 0.27 (hexane:ethyl acetate=1:1)

[1443] NMR (CDCl₃): δ7.70-6.88 (13H, m), 5.01 (1H, dd, J=8.1, 5.4 Hz),4.50-4.40 (2H, m), 4.40-4.31 (2H, m), 3.76-3.70 (2H, m).

EXAMPLE 20 (25)7-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1444]

[1445] TLC: Rf 0.46 (ethyl acetate);

[1446] NMR (CDCl₃): δ 7.75-7.40 (7H, m), 7.07 (1H, d, J=8.0 Hz), 5.05(1H, dd, J=8.4,5.4 Hz), 4.26 (2H, t, J=5.8 Hz), 3.85-3.65 (4H, m), 2.03(2H, quint, J=5.8 Hz).

EXAMPLE 20 (26a)7-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1447]

[1448] TLC: Rf 0.30 (ethyl acetate:triethylamine=20:1);

[1449] NMR (DMSO-d₆): δ 8.85-8.75 (2H, m), 8.27 (1H, d, J=7.6 Hz),7.92-7.55 (7H, m), 7.43 (1H, d, J=8.2 Hz), 7.26 (1H, d, J=7.6 Hz), 5.80(1H, dd, J=9.4, 3.2 Hz), 5.51 (2H, s), 3.99 (1H, dd, J=15.3, 9.4 Hz),3.77 (1H, dd, J=15.3, 3.2 Hz).

EXAMPLE 20 (26b)7-(N-Oxidepyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1450]

[1451] TLC: Rf 0.26 (ethyl acetate: methanol triethylamine 16 3 1);

[1452] NMR (DMSO-d₆): δ 5.38 (1H, s), 8.30 (1H, d, J=5.4 Hz), 7.90-7.42(8H, m), 7.39 (1H, d, J=7.8 Hz), 7.23 (1H, d, J=7.8 Hz), 5.78 (1H, dd,J=9.7, 3.4 Hz), 5.39 (2H, s), 3.99 (1 H, dd, J=15, 9.7 Hz), 3.78 (1H,dd, J=15, 3.4 Hz).

EXAMPLE 20 (27)4-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1453]

[1454] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1455] NMR (CDCl₃): δ 1.48 (s, 9H), 3.76 (dd, J-14.9, 9.2 Hz, 1H), 4.16(d, J=16.0 Hz, 1H), 4.25 (dd, J=1.9, 1.2 Hz, 1H), 4.31 (d, J=16.0 Hz,1H), 5.36 (dd, J=9.2, 1.2 Hz, 1H), 6.82 (dd, J=8.1, 0.7 Hz, 1H), 7.35(d, J=7.4 Hz, 1H), 7.44-7.57 (m, 3H), 7.59-7.67 (m, 1H), 7.78-7.83 (m,2H).

EXAMPLE 20 (28)5-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1456]

[1457] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1458] NMR (CDCl₃): δ 1.53 (s, 9H), 3.74 (d-like, J=6 Hz, 2H), 4.67 (m,2H), 5.00 (t, J=6 Hz, 1H), 7.17 (dd, J=8, 2Hz, 1H), 7.45 (d, J=2 Hz,1H), 7.50 (m, 2H), 7.55 (d, J=8 Hz, 1H), 7.66 (m, 3H).

EXAMPLE 20 (31)6-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1459]

[1460] TLC: Rf 0.42 (hexane:ethyl acetate=1:1);

[1461] NMR (CDCl₃): δ 1.48 (s, 3H), 3.67-3.83 (m, 2H), 4.56 (s, 2H),5.00 (dd, J=7.4, 5.6 Hz, 1H), 6.99 (d, J=2.6 Hz, 1H), 7.29 (dd, J=8.8,2.6 Hz, 1H), 7.46-7.53 (m, 2H), 7.61-7.70 (m 2H), 7.89 (d, J=8.8 Hz,1H).

EXAMPLE 20 (30)7-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1462]

[1463] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1464] NMR (CDCl₃): δ 7.70-7.47 (7H, m), 6.91-6.86 (lH, m), 5.02 (1H,dd, J=8.3, 5.6 Hz), 4.64 (2H, s), 3.76-3.72 (2H, m), 1.44 (9H, s).

EXAMPLE 20 (31)4-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1465]

[1466] TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

[1467] NMR (CDCl₃): 3.42-3.56 (m, 1H), 3.63-3.76 (m, 1H), 3.73 (dd,J=15.2, 9.6 Hz, 1H), 4.02-4.34 (m, 2H), 4.10 (dd, J=15.2, 1.2 Hz, 1H),5.29 (dd, J=9.6, 1.2 Hz, 1H), 5.78 (br, 1H), 7.02 (d-like, J=7.5 Hz,1H), 7.22 (d, J=7.5 Hz, 1H), 7.40-7.64 (m, 4H), 7.21-7.76 (m, 2H).

EXAMPLE 20 (32) 4-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1468]

[1469] TLC: Rf 0.30 (hexane:ethyl acetate 1:2);

[1470] NMR (CDCl₃): δ 1.41 (s, 9H), 1.93 (m, 2H), 3.35 (m, 2H), 3.72(dd, J=15.0, 9.0 Hz, 1H), 3.99 (t, J=6.1 Hz, 2H), 4.09 (d, J=15.0 Hz,2H), 4.95 (br, 1H), 5.35 (d, J=9.0 Hz, 1H), 7.02 (d, J=7.5 Hz, 1H), 7.25(d, J=7.5 Hz, 1H), 7.43-7.67 (m, 4H), 7.70-7.75 (m, 2H).

EXAMPLE 20 (33)5-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1471]

[1472] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[1473] NMR (CDCl₃): δ 1.47 (s, 9H), 3.54 (m, 2H), 3.66 (dd, J=15, 8Hz,1H), 3.80 (dd, J=15,5 Hz, 1H), 4.13 (t, J=5 Hz, 2H), 5.00 (dd, J=8, 5Hz, 1H), 5.00 (br, 1H), 7.12 (dd, J=8, 2 Hz, 1H), 7.44 (d, J-2 Hz, 1H),7.55 (m, 3H), 7.72 (m, 3H).

EXAMPLE 20 (34)6-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1474]

[1475] TLC: Rf 0.41 (hexane:ethyl acetate=1:2);

[1476] NMR (CDCl₃): δ 1.44 (s, 9H), 2.01 (quint, J=6.2 Hz, 2H), 3.32 (q,J=6.2 Hz, 2H), 3.71 (dd, J=14.6, 7.7 Hz, 1H), 3.79 (dd, J=14.6, 5.5 Hz,1H), 4.06 (t, J=6.2 Hz, 2H), 4.68 (br, 1H), 5.00 (dd, J=7.7, 5.5 Hz,1H), 7.05 (d, J=2.4 Hz, 1H), 7.23 (dd, J=8.8, 2.4 Hz, 1H), 7.47-7.54 (m,2H), 7.64-7.72 (m, 3H), 7.85 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (35)6-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1477]

[1478] TLC: Rf 0.24 (hexane ethyl acetate=1:1);

[1479] NMR (CDCl₃): δ 1.46 (s, 9H), 3.56 (q, J=5.4 Hz, 2H), 3.71 (dd,J=14.8, 7.7 Hz, 1H), 3.79 (dd, J=14.8, 5.6 Hz, 1H), 4.06 (t, J=5.4 Hz,2H), 4.97 (br, 1H), 5.00 (dd, J=7.7, 5.6 Hz, 1H), 7.05 (d, J=2.6 Hz,1H), 7.24 (dd, J=8.8, 2.6 Hz, 1H), 7.47-7.55 (m, 2H), 7.65-7.72 (m, 3H),7.88 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (36)7-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1480]

[1481] TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

[1482] NMR (CDCl₃): δ 7.72-7.40 (7H, m), 7.04 (1H, d, J=8.2 Hz), 5.22(1H, bs), 5.02 (1H, dd, J=8.7, 5.0 Hz), 4.25-4.10 (2H, m), 3.85-3.65(2H, m), 3.60-3.46 (2H, m), 1.42 (9H, s).

EXAMPLE 20 (37) 4-(N-(t-Butoxycarbonyl)piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1483]

[1484] TLC: Rf 0.19 (hexane:ethyl acetate=1:1);

[1485] NMR (CDCl₃): δ 7.80-7.38 (6H, m), 7.23 (1H, d, J=8 Hz), 7.05 (1H,d, J=8 Hz), 5.23 (1H, d, J=9 Hz), 4.70 -4.45 (1H, m), 4.08 (1H, d, J=15Hz), 3.95-3.60 (2H, m), 3.72 (1H, dd, J=15, 9 Hz), 3.50-3.22 (2H, m),2.15-1.58 (4H, m), 1.48 (9H, s).

EXAMPLE 20 (38)4,7-Bis[(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1486]

[1487] TLC: Rf 0.25 (hexane:ethyl acetate=1:3);

[1488] NMR (CDCl₃): δ 7.77 (2H, d, J=8.2 Hz), 7.70-7.55 (1H, m),7.55-7.40 (2H, m), 6.95 (2H, s), 5.71 (1H, brs), 5.40-5.15 (2H, m),4.20-3.30 (10H, m), 1.43 (18H, s).

EXAMPLE 20 (39) 4-(3-Nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1489]

[1490] TLC: Rf 0.13 (hexane ethyl acetate=1:1);

[1491] NMR (CDCl₃+CD30D): δ 8.35 (1H, s), 8.27 (1H, d, J=8 Hz), 7.87(1H, d, J=8 Hz), 7.80-7.50 (5H, m), 7.50-7.25 (3H, m), 7.13 (1H, d, J=8Hz), 5.36 (1H, d-like, J=9 Hz), 5.25-4.98 (2H, m), 4.11 (1H, dd, J=15, 1Hz), 3.76 (1H, dd, J=15, 9 Hz).

EXAMPLE 214-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1492]

[1493] To a solution of the compound prepared in Example 20 (27) (105mg) in methylene chloride (5 ml), was added trifluoroacetic acid (5 ml)at 0° C. The reaction mixture was stirred at room temperature for 1hour. The reaction mixture was concentrated. The residue wasrecrystallized from diethyl ether to give the compound of the presentinvention (63 mg) having the following physical data.

[1494] TLC: Rf 0.20 (chloroform:methanol=4:1);

[1495] NMR (CDCl₃+CD₃OD): δ 3.79 (dd, J=14.9, 9.0 Hz, 1H), 4.23 (dd,J=14.9, 1.0 Hz, 1H), 4.26 (d, J=16.1 Hz, 1H), 4.43 (d, J=16.1 Hz, 1H),5.45 (dd, J=9.0, 1.0 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 7.36 (d, J=7.6 Hz,1H), 7.45-7.59 (m, 3H), 7.62-7.70 (m, 1H), 7.77-7.81 (m, 2H).

EXAMPLES 21 (1)˜21 (3)

[1496] By the same procedure as described in Example 21 using thecompounds prepared in Examples 20 (28)˜20 (30) instead of the compoundprepared in Example 20 (27), the following compounds of the presentinvention were obtained.

EXAMPLE 21 (1)5-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1497]

[1498] TLC: Rf 0.30 (chloroform:methanol=4:1);

[1499] NMR (CDCl₃+CD₃OD): δ 3.79 (d-like, J=6 Hz, 2H), 4.76 (s, 2H),5.10 (t, J=6 Hz, 1H), 7.20 (dd, J=8, 2 Hz, 1H), 7.39 (d, J=2 Hz, 1H),7.51 (d, J=8 Hz, 1H), 7.55 (m, 2H), 7.69 (m, 3H).

EXAMPLE 21 (2)6-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1500]

[1501] TLC: Rf 0.25 (chloroform:methanol=4:1);

[1502] NMR (CDCl₃+CD₃OD): δ 3.70-3.85 (m, 2H), 4.68 (s, 2H), 5.07(t-like, J=6.6 Hz, 1H), 7.07 (d, J=2.5 Hz, 1H), 7.32 (dd, J=8.8, 2.5 Hz,1H), 7.47-7.55 (m, 2H), 7.63-7.73 (m, 3H), 7.83 (d, J=8.8 Hz, 1H).

EXAMPLE 21 (3)7-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1503]

[1504] TLC: Rf 0.29 (ethyl acetate:acetic acid=10:1);

[1505] NMR (CDCl₃+DMSO-d₆): δ 7.52-7.26 (6H, m), 7.20 (1H, d, J=7.8 Hz),6.77 (1H, d, J=8.2 Hz), 4.98 (1H, dd, J=7.8, 5.6 Hz), 4.52 (2H, s),3.58-3.54 (2H, m).

EXAMPLE 224-(N-Pyridin-3-ylmethyl)carbamoylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1506]

[1507] A suspension of the compound prepared in Example 21 (480 mg) inthionyl chloride (10 ml) was refluxed for 15 minutes. After removingthionylchloride, the residue was dissolved in methylene chloride (5 ml).Thereto was added dropwise a solution of 3-(aminomethyl)pyridine (0.15ml) and triethylamine (1 ml) in methylene chloride (10 ml) under coolingwith ice. The reaction mixture was stirred at room temperature for 2hours. To the reaction mixture was added water. The mixture wasextracted by ethyl acetate. The extract was washed by water, a saturatedaqueous solution of sodium chloride successively, dried over anhydroussodium sulfate and concentrated. The residue was purified with columnchromatography on silica gel (ethyl acetate:triethylamine=100:1) to givethe compound of the present invention (421 mg) having the followingphysical data.

[1508] Free Compound:

[1509] TLC: Rf 0.49 (ethyl acetate:methanol:triethylamine=8:1:1);

[1510] NMR (DMSO-d₆): δ 4.03 (dd, J=14.9, 8.4 Hz, 1H), 4.11 (d, J=14.5Hz, 1H), 4.12 (dd, J=14.9, 1.6 Hz, 1H), 4.33 (dd, J=15.3, 6.0 Hz, 1H),4.44 (dd, J=15.3, 6.0 Hz, 1H), 4.57 (d, J=14.5 Hz, 1H), 6.00 (dd, J=8.4,1.6 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 7.34 (dd, J=8.0, 4.7 Hz, 1H), 7.40(d, J=8.0 Hz, 1H), 7.49-7.54 (m, 2H), 7.63-7.73 (m, 5H), 8.39 (t, J=6.0Hz, 1H), 8.46 (dd, J=4.7, 1.7 Hz, 1H), 8.51 (d, J=1.7 Hz, 1H).

[1511] Hydrochloride:

[1512] TLC: Rf 0.49 (ethyl acetate:methanol:triethylamine=8:1:1);

[1513] NMR (DMSO-d₆): δ 4.04 (dd, J=15.0, 8.7 Hz, 1H), 4.12 (d, J=14.7Hz, 1H), 4.13 (dd, J=1 5.0, 1.5 Hz, 1H), 4.49 (dd, J=1 5.8, 6.2 Hz, 1H),4.57 (dd, J=15.8, 6.2 Hz, 1H), 4.60 (d, J=14.7 Hz, 1H), 6.15 (dd, J=8.7,1.5 Hz, 1H), 7.25 (d, J=8.2 Hz, 1H), 7.40 (d, J=7.6 Hz, 1H), 7.52-7.57(m, 2H), 7.64 (d, J=8.2 Hz, 1H), 7.68-7.74 (m, 3H), 7.93 (dd, J=8.0, 5.5Hz, 1H), 8.37 (d, J=8.0 Hz, 1H), 8.68 (t, J=6.2 Hz, 1H), 8.78 (d, J=5.4Hz, 1H), 8.81 (s 1H).

EXAMPLES 22 (1) And 22 (2)

[1514] By the same procedure as described in Example 22 using acorresponding amine compound instead of 3-(aminomethyl)pyridine, and ifnecessary, by converting into the corresponding salt by a known method,the following compounds of the present invention were obtained.

EXAMPLE 22 (1)4-((2-(N,N-Dimethylamino)ethylamino)carbonylmethyl)oxy-3-phenylsuifonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1515]

[1516] Free Compound:

[1517] TLC: Rf 0.29 (ethyl acetate:methanol: triethylamine=8:1:1);

[1518] NMR (CDCl₃): δ 2.24 (s, 6H), 2.51 (t-like, J=6.0 Hz, 2H), 3.49(m, J=6.0 Hz, 2H), 3.77 (dd, J=15.3, 9.6 Hz, 1H), 4.05 (dd, J=15.3, 1.3Hz, 1H), 4.53 (d, J=14.2 Hz, 1H), 4.64 (d, J=14.2 Hz, 1H), 5.39 (d-like,J=9.0 Hz, 1H); 7.04 (d, J=8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.42-7.48(m, 2H), 7.57 (t, J=8.0 Hz, 1H), 7.59-7.65 (m, 1H), 7.70-7.74 (m, 2H),7.94 (br, 1H).

[1519] hydrochloride:

[1520] TLC: Rf 0.29 (ethyl acetate:methanol:triethylamine=8:1:1);

[1521] NMR (DMSO-d₆): δ 2.76 (s, 6H), 3.14-3.18 (m, 2H), 3.44-3.56 (m,2H), 4.00 (dd, J=15.0, 9.3 Hz, 1H), 4.03 (d, J=14.4 Hz, 1H), 4.17 (d,J=15.0 Hz, 1H), 4.50 (d, J=14.4 Hz, 1H), 6.24 (d-like, J=8.7 Hz, 1H),7.25 (d, J=8.0 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.56-7.62 (m, 2H), 7.64(t, J=8.0 Hz, 1H), 7.70-7.77 (m, 3H), 8.23 (t, J=5.5 Hz, 1H).

EXAMPLE 22 (2)4-((N-Benzyl-2-(N′,N′-dimethylamino)ethylamino)carbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1522]

[1523] TLC: Rf 0.52 (ethyl acetate:methanol:triethylamine=9:1:1);

[1524] NMR (CDCl₃): δ 2.22 (s, 3H), 2.29 (s, 3H), 2.44-2.55 (m, 2H),3.29-3.35 (m, 1H), 3.56-3.60 (m, 1H), 3.73-3.75 (m, 2H), 4.60 (d, J=15.0Hz, 0.5H), 4.67 (s-like, 1H), 4.76 (d, J=15.0 Hz, 0.5H), 4.88 (s, 1H),4.94-5.00 (m, 1H), 5.05 (d, J=15.0 Hz, 0.5H), 5.18 (d, J=15.0 Hz, 0.5H),7.10-7.36 (m, 6H), 7.41-7.53 (m, 4H), 7.61-7.68 (m, 3H).

EXAMPLE 234-(2-Aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[1525]

[1526] By the same procedure as described in Example 7 using thecompound prepared in Example 20 (31) instead of the compound prepared inExample 6 (8), the compound of the present invention having thefollowing physical data was obtained.

[1527] TLC: Rf 0.21 (ethyl acetate: methanol: triethylamine=8:2:1);

[1528] NMR (DMSO-d₆): δ 2.66-2.78 (m, 1H), 3.02-3.12 (m, 1H), 3.83-4.18(m, 4H), 6.23 (d-like, J=6.6 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.39 (d,J=7.6 Hz, 1H), 7.58-7.68 (m, 3H), 7.72-7.79 (m, 3H), 8.02 (br, 2H).

EXAMPLES 23 (1)˜23 (7)

[1529] By the same procedure as described in Example 23 using thecompounds prepared in Examples 20 (32)˜20 (38) instead of the compoundprepared in Example 20 (31), the following compounds of the presentinvention were obtained.

EXAMPLE 23 (1) 4-(3-Aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1530]

[1531] TLC: Rf 0.12 (ethyl acetate:methanol: triethylamine=8:4:1);

[1532] NMR (DMSO-d₆): δ 1.85-1.93 (m, 2H), 2.93 (q, J=6.4 Hz, 2H),3.87-4.08 (m, 2H), 3.97 (dd, J=15.0, 8.4 Hz, 1H), 4.11 (dd, J=15.0, 1.4Hz, 1H), 5.65 (dd, J=8.4, 1.4 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.33 (d,J=7.8 Hz, 1H), 7.59-7.78 (m, 6H), 8.15 (br, 3H).

EXAMPLE 23 (2)5-(2-Aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1533]

[1534] TLC: Rf 0.25 (ethyl acetate methanol triethylamine 8:2:1);

[1535] NMR (DMSO-d₆): δ 7.81-7.72 (m, 4H), 7.66-7.59 (m, 2H), 7.32-7.27(m, 2H), 5.77 (dd, J=9, 3.5 Hz, 1H), 4.27 (m, 2H), 3.94 (dd, J=15, 9 Hz,1H), 3.71 (dd, J=15, 3.5 Hz, 1H), 3.38-3.32 (m, 2H).

EXAMPLE 23 (3)6-(3-Aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1536]

[1537] TLC: Rf 0.40 (ethyl acetate:methanol:triethylamine=8:2 :1);

[1538] NMR (DMSO-d₆): 5 2.05 (quint, J=6.8 Hz, 2H), 2.95 (t, J=6.8 Hz,2H), 3.76 (dd, J=15.2, 3.0 Hz, 1H), 4.00 (dd, J=15.2, 9.4 Hz, 1H), 4.18(t, J=6.8 Hz, 2H), 5.70 (dd, J=9.4, 3.0 Hz, 1H), 7.29-7.38 (m, 2H),7.56-7.67 (m, 3H), 7.76-7.79 (m, 3H), 8.08 (br, 2H).

EXAMPLE 23 (4)6-(2-Aminoethyl)oxy-3-phenylsulfonyl-1,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1539]

[1540] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=9:1:1);

[1541] NMR (DMSO-d₆): δ 3.22 (t, J=4.9 Hz, 2H), 3.79 (dd, J=15.1, 3.0Hz, 1H), 4.01 (dd, J=15.1, 9.4 Hz, 1H), 4.32 (t, J=4.9 Hz, 2H), 5.73(dd, J=9.4, 3.0 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.40 (dd, J=8.8, 2.4Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.64-7.66 (m, 2H), 7.76-7.81 (m, 3H),8.35 (br, 3H).

EXAMPLE 23 (5)7-(2-Aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1542]

[1543] TLC: Rf 0.38 (ethyl acetate:acetic acid:water=3:1:1);

[1544] NMR (DMSO-d₆): δ 8.18 (3H, brs), 7.83-7.60 (6H, m), 7.40 (1H, d,J=8 Hz), 7.22 (1H, d, J=8 Hz), 5.81 (1 H, dd, J=9.6, 3.2 Hz), 4.44-3.30(2H, m), 3.96 (1 H, dd, J=15, 9.6 Hz), 3.76 (1H, dd, J=15, 3.2 Hz), 3.18(2H, t, J=6 Hz).

EXAMPLE 23 (6)4-(Piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[1545]

[1546] TLC: Rf 0.47 (ethyl acetate:acetic acid:water=3:1:1);

[1547] NMR (DMSO-d₆): δ 8.91 (2H, brs), 7.90-7.52 (6H, m), 7.41 (1H, d,J=8 Hz), 7.33 (1H, d, J=8 Hz), 5.71 (1H, d, J=7 Hz), 4.95-4.70 (1H, m),4.20-3.80 (2H, m), 3.50-2.95 (4H, m), 2.30-1.60 (4H, m).

EXAMPLE 23 (7)4,7-Bis[(2-aminoethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[1548]

[1549] TLC: Rf 0.22 (ethyl acetate:methanol:triethylamine=4:1:1);

[1550] NMR (DMSO-d₆): δ 8.10 (6H, brs), 7.85-7.70 (3H, m), 7.70-7.50(2H, m), 7.37 (1H, d, J=8.6 Hz), 7.23 (1H, d, J=8.6 Hz), 6.14 (1H, d,J=6.0 Hz), 4.50-4.15 (2H, m), 4.15-3.90 (4H, m), 3.85-3.65 (1H, m),3.25-3.15 (2H, m), 3.15-2.90 (1H, m).

EXAMPLE 244-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1551]

[1552] By the same procedure as described in Example 8 using thecompound prepared in Example 23 instead of the compound prepared inExample 7, the compounds of the present invention having the followingphysical data were obtained.

[1553] Free Compound:

[1554] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:2:1);

[1555] NMR (CDCl₃): δ 2.33 (s, 6H), 2.52-2.77 (m, 2H), 3.72 (dd, J=15.0,9.4 Hz, 1H), 3.79-3.89 (m, 1H), 4.00-4.12 (m, 1H), 4.18 (dd, J=15.0, 1.1Hz, 1H), 5.35 (d-like, J=8.8 Hz, 1H), 6.99 (d, J=8.2 Hz, 1H), 7.28 (d,J=7.2 Hz, 1H), 7.43-7.66 (m, 4H), 7.72-7.77 (m, 2H).

[1556] Hydrochloride:

[1557] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:2:1);

[1558] NMR (CD₃OD): δ 3.05 (s, 6H), 3.52-3.76 (m, 2H), 3.83-3.99 (m,2H), 4.38-4.63 (m, 2H), 5.89 (t, J=5.4 Hz, 1H), 7.30 (d, J=7.7 Hz, 1H),7.39 (d, J=7.7 Hz, 1H), 7.51-7.59 (m, 2H), 7.66-7.78 (m, 4H).

EXAMPLES 24 (1)˜24 (5)

[1559] By the same procedure as described in Example 14 using thecompounds prepared in Examples 23 (1)˜23 (5) instead of the compoundprepared in Example 23, and if necessary, by converting into thecorresponding salts by known methods, the following compounds of thepresent invention were obtained, with the proviso that when compounds ofExample 23 (1) and Example 23 (3) were used, compounds of Example 24(1b) and Example 24 (3b) were also generated respectively.

EXAMPLE 24 (1a)4-(3-(N,N-Dimethylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1560]

[1561] Free Compound:

[1562] TLC: Rf 0.35 (ethyl acetate:methanol:triethylamine=8:2:1);

[1563] NMR (CDCl₃): δ 1.86 (quint, J=7.0 Hz, 2H), 2.26 (s, 6H), 2.47 (t,J=7.0 Hz, 2H), 3.74 (dd, J=5.0, 9.2 Hz, 1H), 3.83-4.03 (m, 2H), 4.21(dd, J=15.0, 1.2 Hz, 1H), 5.25 (d-like, J=8.8 Hz, 1H), 6.99 (d, J=7.8Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 7.48-7.74 (m, 6H).

[1564] Hydrochloride:

[1565] TLC: Rf 0.35 (ethyl acetate:methanol:triethylamine=8:2:1);

[1566] NMR (DMSO-d₆): δ 2.15 (m, 2H), 2.80 (s, 6H), 3.31 (t, J=7.5 Hz,2H), 3.75 (dd, J=15.2, 9.2 Hz, 1H), 4.15 (t, J=6.2 Hz, 2H), 4.31 (dd,J=15.2, 1.1 Hz, 1H), 5.69 (dd, J=9.2, 1.1 Hz, 1H), 7.32-7.39 (m, 2H),7.55-7.72 (m, 3H), 7.80-7.85 (m, 3H).

EXAMPLE 24 (1b)4-(3-(N-Cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1567]

[1568] TLC: Rf 0.36 (ethyl acetate:triethylamine=9:1);

[1569] NMR (CDCl₃): δ 1.88 (quint, J=6.6 Hz, 2H), 2.38 (s, 3H), 2.69 (m,2H), 3.51 (d, J=17.0 Hz, 1H), 3.61 (d, J=17.0 Hz, 1H), 3.73 (dd, J=15.0,9.4 Hz, 1H), 3.96 (m, 2H), 4.13 (dd, J=15.0, 1.0 Hz, 1H), 5.28 (d-like,J=8.4 Hz, 1H), 7.00 (d, J=7.8 Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 7.42-7.74(m, 6H).

EXAMPLE 24 (2)5-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydeo-1,1-dioxidebenzo[b]thiophene

[1570]

[1571] Free Compound:

[1572] TLC: Rf 0.55 (ethyl acetate: methanol: triethylamine 8:2:1);

[1573] NMR (DMSO-d₆): δ 2.23 (s, 6H), 2.66 (t, J=6 Hz, 2H), 3.77 (dd,J=15, 3 Hz, 1H), 3.98 (dd, J=15, 10 Hz, 1H), 4.10 (m, 2H), 5.71 (dd,J=10, 3 Hz, 1H), 7.05 (d, J=2 Hz, 1H), 7.25 (dd, J=9, 2 Hz, 1H),7.58-7.84 (m, 6H).

[1574] Hydrochloride:

[1575] TLC: Rf 0.55 (ethyl acetate:methanol:triethylamine=8:2:1);

[1576] NMR (DMSO-d₆): δ 2.84 (s, 6H), 3.56 (m, 2H), 3.75 (dd, J=15, 4Hz, 1H), 3.97 (dd, J=15, 9 Hz, 1H), 4.45 (m, 2H), 5.76 (dd, J=9, 4 Hz,1H), 7.22 (d, J=2 Hz, 1H), 7.33 (dd, J=9, 2 Hz, 1H), 7.64 (m, 2H), 7.79(m, 4H).

EXAMPLE 24 (3a) 6-(3-(N,N-Dimethylamino) propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1577]

[1578] Free Compound:

[1579] TLC: Rf 0.53 (ethyl acetate:methanol:triethylamine=8:2:1);

[1580] NMR (CDCl₃): δ 1.97 (quint, J=6.6 Hz, 2H), 2.25 (s, 6H), 2.44 (t,J=6.6 Hz, 2H), 3.71 (dd, J=14.6, 7.6 Hz; 1H), 3.79 (dd, J=14.6, 5.6 Hz,1H), 4.07 (t, J=6.6 Hz, 2H), 5.00 (dd, J=7.6, 5.6 Hz, 1H), 7.08 (d,J=2.6 Hz, 1H), 7.23 (dd, J=8.8, 2.6 Hz, 1H), 7.46-7.54 (m, 2H),7.63-7.72 (m, 3H), 7.85 (d, J=8.8 Hz, 1H).

[1581] Hydrochloride:

[1582] TLC: Rf 0.53 (ethyl acetate:methanol:triethylamine=8:2:1);

[1583] NMR (DMSO-d₆): δ 2.17 (m, 2H), 2.78 (s, 6H), 3.20 (t, J=7.9 Hz,2H), 3.77 (dd, J=15.4, 3.2 Hz, 1H), 4.00 (dd, J=15.4, 9.4 Hz, 1H), 4.18(t, J=6.0 Hz, 2H), 5.71 (dd, J=9.4, 3.2 Hz, 1H), 7.30-7.38 (m, 2H),7.58-7.67 (m, 3H), 7.75-7.79 (m, 3H).

EXAMPLE 24 (3b) 6-(3-(N-Cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1584]

[1585] TLC: Rf 0.33 (ethyl acetate:hexane:triethylamine=6:3:1);

[1586] NMR (CDCl₃): δ 1.97 (quint, J=6.5 Hz, 2H), 2.38 (s, 3H), 2.65 (t,J=6.5 Hz, 2H), 3.54 (s, 2H), 3.71 (dd, J=14.8, 7.8 Hz, 1H), 3.79 (dd,J=14.8, 5.2 Hz, 1H), 4.06 (t, J=6.5 Hz, 2H), 5.00 (dd, J=7.8, 5.2 Hz,1H), 7.07 (d, J=2.6 Hz, 1H), 7.23 (dd, J=9.0, 2.6 Hz, 1H), 7.47-7.55 (m,2H), 7.65-7.72 (m, 3H), 7.84 (d, J=9.0 Hz, 1H).

EXAMPLE 24 (4) 6-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1587]

[1588] Free Compound:

[1589] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine 9:1:1);

[1590] NMR (CDCl₃): δ 2.34 (s, 6H), 2.75 (t, J=5.4 Hz, 2H), 3.74 (dd,J=14.8, 7.8 Hz, 1H), 3.79 (dd, J=14.8, 5.4Hz, 1H), 4.09 (t, J=5.4 Hz,2H), 5.00 (dd, J=7.8, 5.4Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 7.28 (dd,J=8.8, 2.4 Hz, 1H), 7.47-7.52 (m, 2H), 7.62-7.69 (m, 3H), 7.84 (d, J=8.8Hz, 1H).

[1591] Hydrochloride:

[1592] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=9:1:1);

[1593] NMR (DMSO-d₆): δ 2.83 (d, J=4.5 Hz, 6H), 3.50-3.54 (m, 2H), 3.78(dd, J=15.0, 3.0 Hz, 1H), 4.01 (dd, J=15.0, 9.4 Hz, 1H), 4.49 (t, J=5.1Hz, 2H), 5.73 (dd, J=9.4, 3.0 Hz, 1H), 7.41-7.44 (m, 2H), 7.60-7.67 (m,3H), 7.77-7.80 (m, 3H), 10.83 (br, 1H).

EXAMPLE 24 (5)7-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzp[b]thiophenehydrochloride

[1594]

[1595] TLC: Rf 0.32 (ethyl acetate:methanol:triethylamine=16:3:1);

[1596] NMR (DMSO-d₆): δ 7.85-7.60 (6H, m), 7.37 (1H, d, J=8.2 Hz), 7.22(1H, d, J=8.2 Hz), 5.81 (1 H, dd, J=9.4, 3.2 Hz), 4.65-4.56 (2H, m),3.97 (1H, dd, J=15, 9.4 Hz), 3.75 (1 H, dd, J=15, 3.2 Hz), 3.56-3. 45(2H, m), 2.82 (6H, s).

EXAMPLE 254-(3-Aminophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1597]

[1598] By the same procedure as described in Example 11 using thecompound prepared in Example 20 (39) instead of the compound prepared inExample 10, the compound of the present invention having the followingphysical data was obtained.

[1599] TLC: Rf 0.34 (chloroform:tetrahydrofuran:28% ammoniawater=100:50:1);

[1600] NMR (DMSO-d₆): δ 7.80-7.55 (4H, m), 7.49 (2H, t, J=8 Hz), 7.31(2H, dd, J=12, 8 Hz), 7.02 (1H, t, J=8 Hz), 6.60-6.45 (2H, m), 5.54 (1H,d, J=9 Hz), 5.10 (2H, bs), 4.91 (1H, d, J=12 Hz), 4.69 (1H, d, J=12 Hz),4.20 (1H, d, J=15 Hz), 3.98 (1H, dd, J=15, 9 Hz).

EXAMPLE 264-(3-(Pyridin-3-ylcarbonylamino)phenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1601]

[1602] To a solution of the compound prepared in Example 25 (143 mg) inpyridine (6 ml) was added nicotinyl chloride-hydrochloride (77 mg). Themixture was stirred at room temperature for 1.5 hours. To the reactionmixture, water was added. The mixture was extracted by ethyl acetate.The extract was washed by water, a saturated aqueous solution of sodiumchloride successively, dried over anhydrous sodium sulfate andconcentrated. The residue was recrystallized from ethanol to give thecompound of the present invention (127 mg) having the following physicaldata.

[1603] TLC: Rf 0.34 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1604] NMR (DMSO-d₆): δ 9.12 (1H, d, J=2 Hz), 8.77 (1H, dd, J=5,2 Hz),8.31 (1H, d, J=8 Hz), 7.82 (1H, s), 7.78-7.52 (7H, m), 7.52-7.25 (5H,m), 7.19 (1H, d, J=7 Hz), 5.59 (1H, d, J=8.5 Hz), 5.11 (1H, d, J=12 Hz),4.86 (1H, d, J=12 Hz), 4.20 (1H, d, J=15 Hz), 4.01 (1H, dd, J=15, 8.5Hz).

EXAMPLE 26 (1)4-(2-(Pyridin-3-ylcarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1605]

[1606] By the same procedure as described in Example 26 using thecompound prepared in Example 23 instead of the compound prepared inExample 25, and if necessary, by converting into the corresponding saltby known methods, the compounds of the present invention having thefollowing physical data were obtained.

[1607] Free Compound:

[1608] TLC: Rf 0.43 (ethyl acetate:methanol:triethylamine=8:1:1);

[1609] NMR (DMSO-d₆): δ 3.36-3.55 (m, 2H), 3.81-3.88 (m, 1H), 4.02 (dd,J=15.0, 8.7 Hz, 1H), 4.04-4.10 (m, 1H), 4.13 (dd, J=15.0, 1.3 Hz, 1H),5.61 (d-like, J=7.5 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 7.35 (d, J=7.2 Hz,1H), 7.48 (dd, J=8.1, 4.8 Hz, 1H), 7.56-7.68 (m, 3H), 7.71-7.77 (m, 3H),8.15 (dt, J=8.1, 1.8 Hz, 1H), 8.65-8.68 (m, 1H), 8.68 (dd, J=4.8, 1.8Hz, 1H), 8.98 (d, J=1.8 Hz, 1H).

[1610] Hydrochloride:

[1611] TLC: Rf 0.43 (ethyl acetate:methanol:triethylamine=8:1:1);

[1612] NMR (DMSO-d₆): δ 3.41-3.56 (m, 2H), 3.83-3.89 (m, 1H), 4.01 (dd,J=15.0, 8.7 Hz, 1H), 4.07-4.12 (m, 1H), 4.12 (dd, J=15.0, 1.2 Hz, 1H),5.67 (d-like, J=7.5 Hz, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.34 (d, J=8.0 Hz,1H), 7.56-7.61 (m, 2H), 7.65 (t, J=8.0 Hz, 1H), 7.71-7.76 (m, 3H), 7.83(dd, J=8.1, 5.4 Hz, 1H), 8.59 (dt, J=8.1, 1.6 Hz, 1H), 8.87 (dd, J=5.4,1.6 Hz, 1H), 9.10 (t, J=5.4 Hz, 1H), 9.19 (d, J=1.6 Hz, 1H).

EXAMPLE 275-Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1613]

[1614] To a solution of 5-methyl-1,1-dioxidebenzo[b]thiophene (353 mg)in ethanol (19.5 ml), were added water (0.5 ml), acetic acid (0.4 ml)and benzenesulfonic acid sodium salt (940 mg) successively. The reactionmixture was refluxed for 7 hours. The reaction mixture was cooled toroom temperature. The crystals that appeared were separated byfiltration. The crystals were washed by water, ethanol and hexane,sucessively, to give the compound of the present invention (381 mg)having the following physical data.

[1615] TLC: Rf 0.32 (hexane:ethyl acetate=1:1);

[1616] NMR (CDCl₃): δ 2.52 (s, 3H), 3.66 (dd, J=14.6, 8.7 Hz, 1H), 3.77(dd, J=14.6, 4.9 Hz, 1H), 5.02 (dd, J=8.7, 4.9 Hz, 1H), 7.41-7.57 (m,4H), 7.64-7.69 (m, 3H), 7.80 (s-like, 1H).

EXAMPLES 27 (1)˜27 (5)

[1617] By the same procedure as described in Example 27 usingcorresponding benzo[b]thiophene compounds instead of5-methyl-1,1-dioxidebenzo[b]thiophene, the following compounds of thepresent invention were obtained.

EXAMPLE 27 (1)5-(4-Chlorophenylcarbonyl)amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1618]

[1619] TLC: Rf 0.27 (methylene chloride ethyl acetate 8:1);

[1620] NMR (DMSO-d₆): δ 3.74 (dd, J=15.1, 3.7 Hz, 1H), 3.95 (dd, J=15.1,9.3 Hz, 1H), 5.83 (dd, J=9.3, 3.7 Hz, 1H), 7.58-7.65 (m, 2H), 7.66 (d,J=8.7 Hz, 2H), 7.73-7.83 (m, 4H), 8.04 (d, J=8.7 Hz, 2H), 8.10 (dd,J=8.8, 2.0 Hz, 1H), 8.40 (d, J=2.0 Hz, 1H), 10.86 (s, 1H).

EXAMPLE 27 (2)4-Cyano-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b][thiophene

[1621]

[1622] TLC: Rf 0.60 (methylene chloride:ethyl acetate=8:1);

[1623] NMR (DMSO-d₆): δ 3.95 (dd, J=15, 10 Hz, 1H), 4.15 (d, J=15 Hz,1H), 5.80 (d, J=10 Hz, 1H), 7.60-7.80 (m, 2H), 7.80-7.90 (m, 3H), 7.95(t, J=7.5 Hz, 1H), 8.20 (d, J=7.5 Hz, 1H), 8.35 (d, J=7.5 Hz, 1H).

EXAMPLE 27 (3)6-Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1624]

[1625] TLC: Rf 0.44 (hexane ethyl acetate=1:1);

[1626] NMR (DMSO-d₆): δ 3.97 (dd, J=15.3, 3.0 Hz, 1H), 4.16 (dd, J=15.3,9.3 Hz, 1H), 6.00 (dd, J=9.3, 3.0 Hz, 1H), 7.62-7.67 (m, 2H), 7.79-7.83(m, 3H), 8.02 (d, J=8.4 Hz, 1H), 8.61 (s-like, 1H), 8.62 (dd, J=8.4, 2.1Hz, 1H).

EXAMPLE 27 (4)4,7-Dimethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1627]

[1628] TLC: Rf 0.48 (ethyl acetate );

[1629] NMR (DMSO-d₆): δ 3.27 (s, 3H), 3.85 (s, 3H), 3.96 (dd, J=15.2,8.8 Hz, 1H), 4.12 (dd, J=15.2, 1.5 Hz, 1H), 5.49 (dd, J=8.8, 1.5 Hz,1H), 7.12 (d, J=9.0 Hz, 1H), 7.21 (d, J=9.0 Hz, 1H), 7.60-7.78 (m, 5H).

EXAMPLE 27 (5)4,7-Bis(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1630]

[1631] TLC: Rf 0.34 (ethyl acetate:methanol=9:19;

[1632] NMR (DMSO-d₆): 5 1.52-1.57 (m, 2H), 1.83 (quint, J_6.3 Hz, 2H),3.43 (q, J=6.3 Hz, 2H), 3.55 (q, J=5.8 Hz, 2H), 3.60-3.67 (m, 1H),3.80-3.87 (m, 1H), 3.96 (dd, J=14.8, 9.0 Hz, 1H), 4.09 (d-like, J=14.8Hz, 1H), 4.08-4.21 (m, 2H), 4.46 (t, J=5.1 Hz, 1H), 4.52 (t, J=5.1 Hz,1H), 5.45 (d-like, J=7.8 Hz, 1H), 7.14 (d, J=9.0 Hz, 1H), 7.20 (d, J=9.0Hz, 1H), 7.58-7.63 (m, 2H), 7.72-7.77 (m, 3H).

EXAMPLE 28 4-(Pyridin-3-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1633]

[1634] To 4-carboxy-1,1-dioxidebenzo[b]thiophene (prepared by the methoddescribed in Example 107 hereafter) (270 mg), was added thionyl chloride(2.0 ml). The mixture was refluxed for 2 hours, and concentrated. To asolution of (pyridin-3-ylmethyl)amine (154 mg) dissolved in methylenechloride (6.0 ml) and triethylamine (260 mg), a solution of the saidchloride in methylene chloride (4.0 ml) were added dropwise. The mixturewas stirred for 2 hours at room temperature. To the reaction mixture,ice-water and a 1N aqueous solution of sodium hydroxide (1.5 ml) wereadded dropwise. The mixture was extracted by ethyl acetate (40 ml). Theextract was washed by a saturated sodium chloride, dried over anhydrousmagnesium sulfate, and concentrated. The residue was recrystallized froma mixed solvent of ethyl acetate and hexane to give the compound of thepresent invention (330 mg) having the following physical data.

[1635] TLC: Rf 0.48 (methylene chloride: methanol=10:1);

[1636] NMR (CDCl₃): δ 8.56 (d, J=2.1 Hz, 1H), 8.53 (dd, J=4.5, 2.1 Hz,1H), 7.93 (dd, J=7.2, 0.6 Hz, 1H), 7.79-7.72 (m, 2H), 7.70 (dd, J=7.5,0.6 Hz, 1H), 7.55 (t, J=7.8 Hz, 1H), 7.31 (dd, J=7.8, 4.5 Hz, 1H), 6.86(t, J=6.3 Hz, 1H), 6.77 (d, J=7.2 Hz, 1H), 4.65 (d, J=6.3 Hz, 2Hz.

EXAMPLES 28 (1)˜28 (33)

[1637] By the same procedure as described in Example 28 using carboxylicacid corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and aminederivative corresponding to (pyridin-3-ylmethyl)amine, and if necessary,by converting into the corresponding salt by a known method, thecompounds of the present invention were obtained.

[1638] In the preparation of a compound of Example 28 (33),4-aminomethyl-1,1-dioxidebenzo[b]thiophene and pyridin-3-ylcarboxylicacid were subjected to reaction.

EXAMPLE 28 (1) 4-(4-Benzylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[1639]

[1640] TLC: Rf 0.30 (ethyl acetate:methanol=50:1);

[1641] NMR (CDCl₃): δ 7.75 (d, J=7.4 Hz, 1H), 7.56 (t, J=7.4 Hz, 1H),7.47 (d, J=7.4 Hz, 1H), 7.40-7.20 (m, 6H), 6.78 (d, J=7.0 Hz, 1H), 3.83(m, 2H), 3.55 (s, 2H), 3.34 (m, 2H), 2.55 (m, 2H), 2.37 (m, 2H).

EXAMPLE 28 (2)4-(N-(2-(Pyridin-3-yl)ethyl)-N-methylcarbamoyl)-1,1-dioxidebenzo[b]thiophene

[1642]

[1643] MS (APCI, Pos.): m/z 361 (M+MeOH+H)⁺, 329 (M+H)⁺.

EXAMPLE 28 (3)4-(2-(2-Hydroxyethoxy)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1644]

[1645] MS (APCI, Pos.): m/z 330 (M+MeOH+H)⁺, 298 (M+H)⁺.

EXAMPLE 28 (4)4-(2,4-Dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1646]

[1647] TLC: Rf 0.68 (ethyl acetate);

[1648] NMR (CDCl₃): δ 7.90 (d, J=7.5 Hz, 1H), 7.75 (d, J=7.5 Hz, 1H),7.60 (d, J=7.5 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.25 (d, J=10 Hz, 1H),6.75 (d, J=7.5 Hz, 1H), 6.60-6.40 (m, 3H), 4.55 (d, J=7.5 Hz, 2H), 3.85(s, 3H), 3.80 (s, 3H).

EXAMPLE 28 (5)4-(1-Benzylpiperidin-4-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1649]

[1650] Free Aicd:

[1651] TLC: Rf 0.50 (ethyl acetate:methanol=8:1.5);

[1652] NMR (CDCl₃): δ 7.90 (d, J=7.5 Hz, 1H), 7.80 (d, J=7.5 Hz, 1H),7.60 (d, J=7.5 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.50-7.20 (m, 5H), 6.75(d, J=7.5 Hz, 1H), 6.05-5.95 (m, 1H), 4.10-3.90 (m, 1H), 3.55 (s, 2H),3.00-2.90 (m, 2H), 2.30-2.10 (m, 2H), 2.10-1.90 (m, 2H), 1.70-1.50 (m,2H).

[1653] Hydrochloride:

[1654] TLC: Rf 0.44 (methanol:ethyl acetate=1:10);

[1655] NMR (CD₃OD): δ 7.90-7.75 (m, 3H), 7.75-7.45 (m, 6H), 7.08 (d,J=7.0 Hz, 1H), 4.34 (s, 2H), 4.27-4.05 (m, 1H), 3.61-3.42 (m, 2H),3.33-3.10 (m, 2H), 2.34-2.15 (m, 2H), 2.12-1.81 (m, 2H).

[1656] Methanesulfonic Acid Salt:

[1657] TLC: Rf 0.44 (methanol:ethyl acetate=1:10);

[1658] NMR (CD₃OD): δ 7.89-7.74 (m, 3H), 7.73-7.60 (m, 1H), 7.60-7.45(m, 5H), 7.08 (d, J=7.0 Hz, 1H), 4.34 (s, 2H), 4.27-4.03 (m, 1H),3.68-3.38 (m, 2H), 3.38-3.06 (m, 2H), 2.67 (s, 3H), 2.38-1.72 (m, 4H).

EXAMPLE 28 (6)4-(Pyridin-4-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1659]

[1660] TLC: Rf 0.29 (ethyl acetate:methanol=19:1);

[1661] NMR (CDCl₃+CD₃OD): δ 8.50 (d, J=7 Hz, 2H), 8.25 (broad-t, J=7 Hz,1H), 7.95 (d, J=7 Hz, 1H), 7.80 (d, J=8 Hz, 2H), 7.60 (t, J=8 Hz, 1H),7.30 (d, J=7Hz, 2H), 6.80 (d, J=7 Hz, 1H), 4.60 (d, J=7 Hz, 2H).

EXAMPLE 28 (7) 4-(2-t-Butoxycarbonylethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1662]

[1663] TLC: Rf 0.40 (ethyl acetate:hexane=3:2);

[1664] NMR (CDCl₃): δ 8.00 (d, J=7 Hz, 1H), 7.80 (d, J=8 Hz, 1H), 7.70(d, J=8 Hz, 1H), 7.60 (t, J=8 Hz, 1H), 6.95 (broad-s, 1H), 6.80 (d, J=7Hz, 1H), 3 70 (q, J=7 Hz, 7H), 2.60 (t, J=7 Hz, 2H), 1.45 (s, 9H).

EXAMPLE 28 (8)4-(Thiophen-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1665]

[1666] TLC: Rf 0.48 (chloroform:methanol=9:1);

[1667] NMR (CDCl₃+DMSO-d₆): δ 8.50 (t, J=7 Hz, 1H), 7.95 (d, J=6 Hz,1H), 7.85 (d, J=8 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H),7.25 (d, J=6 Hz, 1H), 7.05 (d, J=3 Hz, 1H), 6.95 (dd, J=3 Hz and 6 Hz,1H), 6.80 (d, J=6 Hz, 1H), 4.75 (d, J=7 Hz, 2H).

EXAMPLE 28 (9) 4-Benzylcarbamoyl-1,1-dioxidebenzo[b]thiophene

[1668]

[1669] TLC: Rf 040 (ethyl acetate hexane=1:1);

[1670] NMR (CDCl₃+DMSO-d₆): δ 7.99 (d, J=7.2 Hz, 1H), 7.81-7.75 (m, 2H),7.56 (t, J=7.5 Hz, 1H), 7.43 (t, J=5.7 Hz, 1H), 7.40-7.27 (m, 5H), 6.78(d, J=7.2 Hz, 1H), 4.63 (d, J=5.7 Hz, 2H).

EXAMPLE 28 (10)4-(Pyridin-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1671]

[1672] TLC: Rf 0.30 (ethyl acetate:hexane=1:1);

[1673] NMR (CDCl₃): δ 8.56 (d, J=5.1 Hz, 1H), 8.05 (dd, J=7.2, 0.9 Hz,1H), 7.84 (t, J=7.2 Hz, 1H), 7.73 (dt, J=0.9, 7.8 Hz, 1H), 7.68 (t,J=5.1 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.33 (d, J=7.8 Hz, 1H), 7.59-7.23(m, 2H), 6.78 (d, J=6.9 Hz, 1H), 4.76 (d, J=5.1 Hz, 2H).

EXAMPLE 28 (11)4-(2-(Piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1674]

[1675] Free Aicd:

[1676] TLC: Rf 0.35 (methylene chloride:methanol=10:1);

[1677] NMR (CDCl₃): δ 8.04 (dd, J=7.2, 0.9 Hz, 1H), 7.80 (dt, J=7.8. 0.9Hz, 1H), 7.72 (dd. J=7.8, 0.9 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.02 (bs,1H), 6.77 (d, J=7.2 Hz, 1H), 3.54 (q, J=5.7 Hz, 2H), 2.58 (t, J=5.7 Hz,2H), 2.50-2.40 (m, 4H), 1.76-1.43 (m, 6H).

[1678] Hydrochloride:

[1679] TLC: Rf 0.60 (methylenechloride:methanol:triethylamine=8:1.5:0.5);

[1680] NMR (DMSO-d₆): δ 10.20 (br. s, 1H), 9.25-9.10 (m, 1H), 8.01 (d,J=7.0 Hz, 1H), 7.99 (d, J=7.0 Hz, 1H), 7.93 (d, J=6.9 Hz, 1H), 7.73 (t,J=7.0 Hz, 1H), 7.47 (d, J=6.9 Hz, 1H), 3.80-3.60 (m, 2H), 3.60-3.50 (m,2H), 3.45-3.15 (m, 2H), 3.10-2.80 (m, 2H), 2.00-1.70 (m, 5H), 1.55-1.30(m, 1H).

EXAMPLE 28 (12)4-((1S)-1-t-Butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1681]

[1682] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[1683] NMR (CDCl₃): δ 7.95 (d, J=7.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H),7.77 (d, J=7.8 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 6.78 (d, J=7.2 Hz, 1H),6.56 (d, J=8.4 Hz, 1H), 4.64 (dd, J=8.4, 4.2 Hz, 1H), 2.36-2.27 (m, 1H),1.51 (s, 9H), 1.02 (d, J=6.9 Hz, 3H), 0.98 (d, J=6.9 Hz, 3H).

EXAMPLE 28 (13)4-(2-Fluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1684]

[1685] TLC: Rf 0.60 (chloroform:methanol=9:1);

[1686] NMR (CDCl₃+DMSO-d₆): δ 7.95 (broad peak, 1H), 7.95 (d, J=7 Hz,1H), 7.80 (d, J=8 Hz, 1H), 7.78 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H),7.50-7.20 (m, 2H), 7.20-7.00 (m, 2H), 6.77 (d, J=7 Hz, 1H), 4.62 (d, J=7Hz, 2H).

EXAMPLE 28 (14)4-(3-Fluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1687]

[1688] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1689] NMR (CDCl₃+DMSO-d₆): δ 8.40 (broad peak, 1H), 7.98 (d, J=7 Hz,1H), 7.85 (d, J=8 Hz, 1H), 7.80 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H),7.40-7.25 (m, 1H), 7.20-6.90 (m, 3H), 6.80 (d, J=7 Hz, 1H), 4.60 (d, J=7Hz, 2H).

EXAMPLE 28 (15)4-(3-Methylphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1690]

[1691] TLC: Rf 0.60 (chloroform: methanol=9:1); NMR (CDCl₃): δ 7.95 (d,J=7 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.65 (d, J=8 Hz, 1H), 7.52 (t, J=8Hz, 1H), 7.30-7.20 (m, 1H), 7.20-7.10 (m, 3H), 6.75 (d, J=7 Hz, 1H),6.40 (broad peak, 1H), 4.60 (d, J=7 Hz, 2H), 2.40 (s, 3H).

EXAMPLE 28 (16)4-(2-Methoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1692]

[1693] TLC: Rf 0.64 (chloroform:methanol=9:1);

[1694] NMR (CDCl₃+DMSO-d₆): δ 7.93 (d, J=7 Hz, 1H), 7.85-7.70 (m, 3H),7.55 (t, J=8 Hz, 1H), 7.30 (m, 2H), 6.92 (m, 2H), 6.78 (d, J=7 Hz, 1H),4.60 (d, J=7 Hz, 2H), 3.90 (s, 3H).

EXAMPLE 28 (17)4-(2,3-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1695]

[1696] TLC: Rf 0.63 (chloroform:methanol=9:1);

[1697] NMR (CDCl₃+DMSO-d₆): δ 7.97 (d, J=7.2 Hz, 1H), 7.77 (d, J=7.6 Hz,1H), 7.76 (d, J=7.6 Hz, 1H), 7.73 (broad peak, 1H), 7.54 (t, J=7.6 Hz,1H), 7.06 (t, J=7.8 Hz, 1H), 7.00-6.85 (m, 2H), 6.77 (d, J=7.2 Hz, 1H),4.63 (d, J=5.6 Hz, 2H), 3.90 (s, 3H), 3.88 (s, 3H).

EXAMPLE 28 (18)4-(3,4-Dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1698]

[1699] TLC: Rf 0.53 (chloroform:methanol=9:1);

[1700] NMR (CDCl₃+DMSO-d₆): δ 8.57 (t-like, J=5.8 Hz, 1H), 7.97 (d,J=7.2 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz,1H), 7.57 (t,J=7.8 Hz,1H), 7.00-6.80 (m, 4H), 4.53 (d, J=5.8 Hz, 2H), 3.88 (s, 3H),3.87 (s, 3H).

EXAMPLE 28 (19)4-(2,5-Difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1701]

[1702] TLC: Rf 0.45 (chloroform:methanol 9:1);

[1703] NMR (CDCl₃+DMSO-d₆): δ 8.78 (t, J=6.0 Hz, 1H), 7.97 (dd, J=7.0 Hzand 1.0 Hz, 1H), 7.89 (dd, J=7.6 Hz and 1.0 Hz, 1H), 7.79 (d, J=7.6 Hz,1H), 7.59 (t, J=7.6 Hz, 1H), 7.20-6.90 (m, 3H), 6.82 (d, J=7.0 Hz, 1H),4.60 (d, J=6.0 Hz, 1H).

EXAMPLE 28 (20)4-(3,4,5-Trimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1704]

[1705] TLC: Rf 0.33 (chloroform:methanol=9:1);

[1706] NMR (CDCl₃, DMSO-d₆): δ 8.00 (broad peak, 1H), 7.98 (dd, J=7.2 Hzand 1.0 Hz, 1H), 7.82 (dd, J=7.6 Hz and 1.0 Hz, 1H), 7.78 (d, J=7.6 Hz,1H), 7.56 (t, J=7.6 Hz, 1H), 6.79 (d, J=7.2 Hz, 1H), 6.61 (s, 2H), 4.54(d, J=5.8 Hz, 2H), 3.86 (s, 6H), 3.83 (s, 3H).

EXAMPLE 28 (21)4-(Benzimidazol-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1707]

[1708] TLC: Rf 0.28 (chloroform:methanol=9:1);

[1709] NMR (CDCl₃+DMSO-d6): δ 8.97 (t, J=5.6 Hz, 1H), 8.08 (d, J=7.2 Hz,1H), 7.94 (dd, J=7.8 Hz and 1.0 Hz, 1H), 7.79 (dd, J=7.8 Hz and 1.0 Hz,1H), 7.62-7.50 (m, 3H), 7.30-7.15 (m, 2H), 6.81 (d, J=7.2 Hz, 1H), 4.85(d, J=5.6 Hz, 2H).

EXAMPLE 28 (22)4-(3,5-Difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1710]

[1711] TLC: Rf 0.57 (chloroform:methanol=9:1);

[1712] NMR (CDCl₃+DMSO-d₆): δ 9.11 (t, J=5.8 Hz, 1H), 7.98 (dd, J=7.2 Hzand 1.0 Hz, 1H), 7.93 (dd, J=7.6 Hz and 1.0 Hz, 1H), 7.81 (d, J=7.6 Hz,1H), 7.62 (t, J=7.6 Hz, 1H), 7.00-6.90 (m, 2H), 6.90 (d, J=7.2 Hz, 1H),6.80-6.68 (m, 1H), 4.55 (d, J=5.8 Hz, 2H).

EXAMPLE 28 (23)4-(N-Benzyl-N-methylcarbamoyl)-1,1-dioxidebenzo[b]thiophene

[1713]

[1714] TLC: Rf 0.69 (chloroform:methanol=9:1);

[1715] NMR (CDCl₃): δ 7.80-7.70 (m, 1H), 7.65-7.47 (m, 2H), 7.47-7.25(m, 5H), 7.15-7.00 (m, 1H), 6.80-6.72 (m, 1H), 4.78 and 4.44 (each s,total 2H), 3.12 and 2.84 (each s, total 3H).

EXAMPLE 28 (24)4-(4-Nitrophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1716]

[1717] TLC: Rf 0.44 (chloroform:methanol 9:1);

[1718] NMR (CDCl₃+DMSO-d₆): δ 9.20 (t, J=5.8 Hz, 1H), 8.20 (d, J=8 Hz,2H), 7.98 (d, J=7 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.81 (d, J=7.5 Hz,1H), 7.62 (t, J=7.5 Hz, 1H), 7.57 (d, J=8 Hz, 2H), 6.89 (d, J=7 Hz, 1H),4.67 (d, J=5.8 Hz, 2H).

EXAMPLE 28 (25) 5-(2-Hydroxyethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1719]

[1720] TLC: Rf 0.38 (ethyl acetate);

[1721] NMR (CDCl₃+CD₃OD): δ 7.98 (dd, J=8.0 Hz, 1.2 Hz, 1H), 7.88 (d,J=1.2 Hz, 1H), 7.77 (d, J=8.0 Hz, 1H), 7.31 (d, J=6.8 Hz, 1H), 6.81 (d,J=6.8 Hz, 1H), 3.78 (t, J=4.8 Hz, 2H), 3.57 (t, J=4.8 Hz, 2H).

EXAMPLE 28 (26)5-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1722]

[1723] MS (APCI, Pos.): m/z 363 (M+MeOH+H)⁺, 331 (M+H)⁺.

EXAMPLE 28 (27)5-(2-Dimethylaminoethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1724]

[1725] TLC: Rf 0.27 (methylene chloride:methanol=10:1);

[1726] NMR (CDCl₃): δ 8.23 (d, J=8.1 Hz,1H), 8.03 (t, J=5.7 Hz, 1H),7.55 (d, J=8.1 Hz, 1H), 7.41 (d, J=6.9 Hz, 1H), 6.76 (d, J=6.9 Hz, 1H),3.94 (s, 3H), 3.57 (q, J=5.7 Hz, 2H), 2.53 (t, J=5.7 Hz, 2H), 2.30 (s,6H).

EXAMPLE 28 (28)5-Dimethylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1727]

[1728] TLC: Rf 0.35 (methanol:ethyl acetate=5:95);

[1729] NMR (CDCl₃): δ 7.52-7.38 (m, 3H), 6.75 (d, J=7.4 Hz, 1H), 3.93(s, 3H), 3.15 (s, 3H), 2.88 (s, 3H).

EXAMPLE 28 (29)5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1730]

[1731] TLC: Rf 0.60 (methylene chloride:methanol=10:1);

[1732] NMR (CDCl₃): δ 7.48 (dd, J=7.5,0.9Hz, 1H), 7.42 (dd, J=6.9, 0.9Hz, 1H), 7.38 (d, J=7.5 Hz, 1H), 6.74 (d, J=6.9 Hz, 1H), 3.95 (s, 3H),3.80-3.56 (m, 2H), 3.30-3.20 (m, 2H), 1.90-1.75 (m, 2H), 1.75-1.40 (m,6H).

EXAMPLE 28 (30)5-(2,3-Dihydroindol-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1733]

[1734] TLC: Rf 0.82 (methylene chloride:methanol=10:1);

[1735] NMR (CDCl₃): δ 8.31 (d, J=7.8 Hz, 1H), 7.54 (s, 2H), 7.45 (d,J=6.9 Hz, 1H), 7.33-7.20 (m, 2H), 7.20-7.07 (m, 1H), 6.77 (d, J=6.9 Hz,1H), 3.97 (s, 3H), 3.90-3.66 (m, 2H), 3.25-3.10 (m, 2H).

EXAMPLE 28 (31)5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1736]

[1737] TLC: Rf 0.30 (ethyl acetate:hexane=1:1);

[1738] NMR (CDCl₃): δ 7.51 (d, J=7.8 Hz, 1H), 7.46 (d, J=7.8 Hz, 1H),7.43-7.35 (m, 2H), 7.30-7.20 (m, 1H), 7.06-6.99 (m, 2H), 6.76 (d, J=6.9Hz, 1H), 4.10-3.90 (m, 2H), 3.98 (s, 3H), 3.54-3.37 (m, 2H),3.20-2.90(m, 4H).

EXAMPLE 28 (32)5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1739]

[1740] TLC: Rf 0.33 (ethyl acetate);

[1741] NMR (CDCl₃): δ 7.63 (d, J=7.8 Hz, 1H), 7.49 (d, J=7.5 Hz, 2H),7.46-7.40 (m, 2H), 7.40-7.27 (m, 2H), 6.75 (d, J=7.5 Hz, 1H), 3.94 (s,3H), 3.90-3.80 (m, 2H), 3.35-3.20 (m, 2H), 3.04-2.94 (m, 2H), 2.68-2.60(m, 4H), 2.58-2.40 (m, 2H).

EXAMPLE 28 (33)4-(Pyridin-3-ylcarbonyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1742]

[1743] MS (APCI, Pos.): m/z 333 (M+MeOH+H)⁺, 301 (M+H)⁺.

EXAMPLE 29 4-(3-(Pyrrol-1-yl)-propyl) oxy-1,1-dioxidebenzo[b]thiophene

[1744]

[1745] 4-Hydroxy-1,1-dioxidebenzo[b]thiophene (370 mg),triphenylphosphine (630 mg) and 1-(3-hydroxypropyl)pyrrole (300 mg) weredissolved in anhydrous tetrahydrofuran (15 ml). Under an atmosphere ofargon to the mixture, was added a solution of diethylazodicarboxylate(323 mg) in anhydrous tetrahydrofuran (4 ml) dropwise. The mixture wasstirred at room temperature for 2 hours. To the reaction mixturemethanol was added. The mixture was stirred for 10 minutes. The reactionmixture was concentrated. The residue was purified with columnchromatography on silica gel (hexane:ethyl acetate=2:1) to give thecompound of the present invention (473 mg) having the following physicaldata.

[1746] TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

[1747] NMR (CDCl₃): δ 7.55-7.35 (m, 2H), 7.30 (d, J=8 Hz, 1H), 6.97 (d,J=8 Hz, 1H), 6.75-6.54 (m, 3H), 6.16 (t, J=2 Hz, 2H), 4.12 (t, J=6 Hz,2H), 4.00 (t, J=6 Hz, 2H), 2.27 (q, J=6 Hz, 2H).

EXAMPLES 30˜30 (13)

[1748] By the same procedure as described in Example 18 using alcoholderivative corresponding to the compound prepared in Example 9 (12) andhalogenated compound corresponding to 4-nitrobenzylbromide, or by thesame procedure as described in Example 29 using alcohol derivativecorresponding to 4-hydroxy-1,1-dioxidebenzo[b]thiophene and alcoholderivative corresponding to 1-(3-hydroxypropyl)pyrrole, the followingcompounds of the present invention were obtained.

EXAMPLE 30 4-(Quinolin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1749]

[1750] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[1751] NMR (CDCl₃): δ 8.23 (d, J=8 Hz, 1H), 8.09 (d, J=8Hz, 1H),7.95-7.68 (m, 2H), 7.68-7.50 (m, 3H), 7.50-7.22 (m, 2H), 7.14 (d, J=8Hz, 1H), 6.66 (d, J=7 Hz, 1H), 5.49 (s, 2H).

EXAMPLE 30 (1) 4-(2-(Pyrrol-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1752]

[1753] TLC: Rf 0.50 (ethyl acetate:hexane=2:1);

[1754] NMR (CDCl₃): δ 7.55-7.22 (m, 3H), 6.94 (d, J=8 Hz, 1H), 6.73 (t,J=2 Hz, 2H), 6.62 (d, J=7 Hz, 1H), 6.19 (t, J=2 Hz, 2H), 4.32 (s, 4H).

EXAMPLE 30 (2)4-(2-(4-Methylazol-5-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1755]

[1756] TLC: Rf 0.15 (ethyl acetate:hexane=2:1);

[1757] NMR (CDCl₃): δ 8.63 (s, 1H), 7.58-7.37 (m, 2H), 7.31 (d, J=8 Hz,1H), 7.03 (d, J=8 Hz,1H), 6.64 (d, J=8 Hz, 1H), 4.26 (t, J=6 Hz, 2H),3.31 (t, J=6 Hz, 2H), 2.46 (s, 3H).

EXAMPLE 30 (3)4-(3-(Pyridin-4-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene

[1758]

[1759] TLC: Rf 0.36 (ethyl acetate:methanol=10:1);

[1760] NMR (CDCl₃): δ 8.53 (dd, J=1.6, 4.5 Hz, 2H), 7.60-7.22 (m, 3H),7.14 (d, J=5.8 Hz, 2H), 7.00 (d, J=8.0 Hz, 1H), 6.62 (d, J=7.4 Hz, 1H),4.09 (t, J=6.2 Hz, 2H), 2.84 (t, J=7.4 Hz, 2H), 2.19 (quint, J=6.2 Hz,2H).

EXAMPLE 30 (4)4-(1-t-Butoxycarbonylpiperidin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1761]

[1762] TLC: Rf 0.46 (hexane:ethyl acetate=1:1);

[1763] NMR (CDCl₃): δ 7.58-7.38 (m, 2H), 7.30 (d, J=7.6 Hz, 1H), 7.04(d, J=8.2 Hz, 1H), 6.61 (d, J=7.0 Hz, 3.15-2.50 (m, 4H), 1.45 (s, 9H).

EXAMPLE 30 (5)4-(2-(Pyrrolidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1764]

[1765] TLC: Rf 0.36 (ethyl acetate:acetic acid:water=3:1:1);

[1766] NMR (CDCl₃): δ 7.55-7.35 (m, 2H), 7.29 (d, J=7 Hz, 1H), 7.06 (d,J=8 Hz, 1H), 6.61 (d, J=7 Hz, 1H), 4.22 (t, J=6 Hz, 2H), 2.94 (t, J=6Hz, 2H), 2.64 (t, J=6 Hz, 4H), 2.20-1.65 (m, 4H).

EXAMPLE 30 (6)4-(2-(Piperidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1767]

[1768] TLC: Rf 0.44 (ethyl acetate:acetic acid:water=3:1:1);

[1769] NMR (CDCl₃): δ 7.60-7.58 (m, 2H), 7.29 (d, J=8 Hz, 1H), 7.07 (d,J=8 Hz, 1H), 6.61 (d, J=7 Hz, 1H), 4.21 (t, J=6 Hz, 2H), 2.80 (t, J=6Hz, 2H), 2.51 (t, J=6 Hz, 4H), 1.90-1.35 (m 6H).

EXAMPLE 30 (7)4-(2-(2-Acetyloxyethoxy)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1770]

[1771] TLC: Rf 0.46 (ethyl acetate:hexane=2:1);

[1772] NMR (CDCl₃): δ 5 7.58-7.38 (m, 2H), 7.31 (d, J=7 Hz, 1H), 7.08(d, J=9 Hz, 1H), 6.62 (d, J=7 Hz, 1H), 4.25 (t, J=5 Hz, 4H), 3.88 (t,J=5 Hz, 2H), 3.76 (t, J=5 Hz, 2H), 2.07 (s, 3H).

EXAMPLE 30 (8)4-(2-(4-Benzylpiperazin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1773]

[1774] TLC: Rf 0.57 (chloroform:methanol 5:1);

[1775] NMR (CDCl₃): δ 7.58-7.38 (m, 2H), 7.38-7.18 (m, 6H), 7.05 (d, J=8Hz, 1H), 6.60 (d, J=7 Hz,1H), 4.35-4.05 (m, 2H), 3.52 (s, 2H), 2.85 (t,J=6 Hz, 2H), 2.78-2.35 (m, 8H).

EXAMPLE 30 (9) 4-Diethylcarbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene

[1776]

[1777] TLC: Rf 0.25 (hexane:ethyl acetate=1:2);

[1778] NMR (CDCl₃): δ 7.52 (d, J=7.0 Hz,1H), 7.46 (t, J=8.0 Hz, 1H),7.32 (d, J=8.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.63 (d, J=7.0 Hz, 1H),4.80 (s, 2H), 3.41 (q, J=7.2 Hz, 2H), 3.36 (q, J=7.2 Hz, 2H), 1.23 (t,J=7.2 Hz, 3H), 1.15 (t, J=7.2 Hz, 3H).

EXAMPLE 30 (10) 4-Cyanomethyloxy-1,1-dioxidebenzo[b]thiophene

[1779]

[1780] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[1781] NMR (CDCl₃): δ 7.65-7.35 (m, 3H), 7.15 (d, J=7.5 Hz, 1H), 6.70(d, J=7.5 Hz, 1H), 4.90 (s, 2H).

EXAMPLE 30 (11)5-(Pyridin-3-yloxy)methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1782]

[1783] MS (APCI, Pos.): m/z 336 (M+MeOH+H)⁺, 304 (M+H)⁺.

EXAMPLE 30 (12)5-(2-t-Butoxycarbonylaminoethyl)oxy-4-nitro-1,1-dioxidebenzo[b]thiophene

[1784]

[1785] TLC: Rf 0.32 (hexane:ethyl acetate=1:1);

[1786] NMR (CDCl₃) δ 7.80 (d, J=8.6 Hz, 1H), 7.33 (d, J=7.0 Hz, 1H),7.18 (d, J=8.6 Hz, 1H), 6.93 (d, J=7.0 Hz, 1H), 5.00 (br, 1H), 4.24 (t,J=5.2 Hz, 2H), 3.57 (q, J=5.2 Hz, 2H), 1.45 (s, 9H).

EXAMPLE 30 (13) 5-((2E)-3-Ethoxycarbonyl-2-propenyl)oxy-1,1-dioxidebenzo[b]thiophene

[1787]

[1788] TLC: Rf 0.51 (hexane:ethyl acetate=1:1);

[1789] NMR (CDCl₃): δ 7.65 (d, J=8.8 Hz, 1H), 7.14 (d, J=6.8 Hz, 1H),7.12-6.85 (m, 4H), 6.74 (d, J=6.8 Hz, 1H), 6.23-6.10 (m, 1H), 4.82-4.73(m, 2H), 4.23 (q, J=7.0 Hz, 2H), 1.31 (t, J=7.0 Hz, 3H).

EXAMPLE 314-(2,4-Dimethoxyphenylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1790]

[1791] 4-Bromomethyl-1,1-dioxidebenzo[b]thiophene (198 mg) was dissolvedin acetonitrile (10 ml). Thereto was added a solution of2,4-dimethoxybenzylamine, hydrochloride (188 mg) and triethylamine (0.26ml) in acetonitrile (6 ml). The mixture was stirred at room temperaturefor 1 hour. To the reaction mixture a saturated aqueous solution ofsodium bicarbonate was added. The mixture was extracted by ethylacetate. The extract was washed by a saturated solution of sodiumchloride, dried over anhydrous sodium sulfate and concentrated. Theresidue was purified with column chromatography on silica gel (ethylacetate:hexane 1:1→2:1) to give the compound of the present invention(113 mg) having the following physical data.

[1792] TLC: Rf 0.29 (ethyl acetate);

[1793] NMR (CDCl₃): δ 7.63-7.39 (m, 4H), 7.07 (d, J=8.0 Hz,1H), 6.66 (d,J=7.0 Hz,1H), 6.49-6.39 (m, 2H), 3.83 (s, 2H), 3.81 (s, 3H), 3.79 (s,3H), 3.72 (s, 2H), 1.98 (s, 1H).

EXAMPLES 31 (1)˜31 (12)

[1794] By the same procedure as described in Example 31 using4-bromomethyl-1,1-dioxidebenzo[b]thiophene and an amine derivativecorresponding to 2,4-dimethoxybenzylamine-hydrochloride, and ifnecessary, by converting into the corresponding salt by a known method,the following compounds of the present invention were obtained.

EXAMPLE 31 (1)4-(Pyridin-3-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[1795]

[1796] TLC: Rf 0.37 (ethyl acetate:methanol=5:1);

[1797] NMR (CD₃OD): δ 9.11 (d, J=1.7 Hz, 1H), 8.92 (dd, J=5.5, 1.7 Hz,1H), 8.73 (dt, J=8.2, 1.7 Hz, 1H), 8.10 (dd, J=8.2, 5.5 Hz, 1H),7.94-7.90 (m, 2H), 7.84 (d, J=7.4 Hz, 1H), 7.20 (t, J=7.4 Hz,. 1H), 7.18(d, J=7.4 Hz, 1H), 4.68 (s, 2H), 4.63 (s, 2H).

EXAMPLE 31 (2)4-(2-(Dimethylamino)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1798]

[1799] MS (APCI, Pos.): mlz 299 (M+MeOH+H)⁺, 267 (M+H)⁺.

EXAMPLE 31 (3)4-(N,N-Bis(2-hydroxyethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene

[1800]

[1801] MS (APCI, Pos.): m/z 316 (M+MeOH+H)⁺, 284 (M+H)⁺.

EXAMPLE 31 (4)4-(2-(2-Hydroxyethoxy)ethyl)aminoethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1802]

[1803] MS (APCI, Pos.): m/z 599 (2M+MeOH+H)⁺, 567 (2M+H)⁺, 316(M+MeOH+H)⁺, 284 (M+H)⁺.

EXAMPLE 31 (5)4-(4-Benzylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1804]

[1805] Free Compound:

[1806] TLC: Rf 0.27 (ethyl acetate:hexane=1:1);

[1807] NMR (CDCl₃): δ 7.71 (d, J=7.0 Hz, 1H), 7.62 (t, J=4.6 Hz, 1H),7.44 (d, J=4.6 Hz, 2H), 7.35-7.25 (m, 5H), 6.68 (d, J=7.0 Hz, 1H), 3.60(s, 2H), 3.51 (s, 2H), 2.46 (brs, 8H).

[1808] 2hydrochloride:

[1809] TLC: Rf 0.32 (ethyl acetate);

[1810] NMR (CD₃OD): δ 7.86 (d, J=7.2 Hz, 1H), 7.76-7.70 (m, 2H), 7.63(d, J=7.8 Hz, 1H), 7.58-7.47 (m, 5H), 7.07 (d, J=7.2 Hz, 1H), 4.38 (s,2H), 4.13 (s, 2H), 3.41 (br, 4H), 3.13 (br, 4H).

EXAMPLE 31 (6)4-(4-(Pyridin-2-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1811]

[1812] MS (APCI, Pos.): m/z 374 (M+MeOH+H)⁺, 342 (M+H)⁺.

EXAMPLE 31 (7)4-(4-Ethoxycarbonylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1813]

[1814] MS (APCI, Pos.): m/z 369 (M+MeOH+H)⁺, 337 (M+H)⁺.

EXAMPLE 31 (8)4-(4-(2-Hydroxyethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1815]

[1816] MS (APCI, Pos.): m/z 649 (2M+MeOH+H)⁺, 617 (2M+H)⁺, 341(M+MeOH+H)⁺, 309 (M+H)⁺.

EXAMPLE 31 (9)4-(4-(Pyridin-4-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1817]

[1818] MS (APCI, Pos.): m/z 374 (M+MeOH+H)⁺, 342 (M+H)⁺.

EXAMPLE 31 (10) 4-Benzylaminomethyl-1,1-dioxidebenzo[b]thiophene

[1819]

[1820] Free Compound:

[1821] TLC: Rf 0.66 (ethyl acetate);

[1822] NMR (CDCl₃): δ 7.62 (d, J=7.2 Hz, 1H), 7.56 (d, J=7.5 Hz, 1H),7.52 (d, J=7.5 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 7.39-7.24 (m, 5H), 6.69(d, J=7.2 Hz, 1H), 3.89 (s, 2H), 3.81 (s, 2H), 1.59 (s, 1H).

[1823] Hydrochloride:

[1824] TLC: Rf 0.47 (ethyl acetate:hexane 2:1);

[1825] NMR (CD₃OD): δ 7.95-7.18 (m, 8H), 7.15 (d, J=7 Hz, 1H), 6.98 (d,J=7 Hz, 1H), 4.48 (s, 2H), 4.36 (s, 2H).

EXAMPLE 31 (11)4-(1-Benzylpiperidin-4-yl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1826]

[1827] Free Compound:

[1828] TLC: Rf 0.27 (ethyl acetate:methanol=4:1);

[1829] NMR (CDCl₃): δ 7.65 (d, J=7.0 Hz, 1H), 7.61 (d, J=6.8 Hz, 1H),7.56-7.40 (m, 2H), 7.34-7.22 (m, 5H), 6.68 (d, J=7.0 Hz, 1H), 3.91 (s,2H), 3.50 (s, 2H), 2.91-2.77 (m, 2H), 2.60-2.43 (m, 1H), 2.12-1.95 (m,2H), 1.95-1.80 (m, 2H), 1.60-1.32 (m, 3H).

[1830] 2hydrochloride:

[1831] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[1832] NMR (DMSO-d₆+CD₃OD): δ 7.97 (d, J=7.2 Hz, 1H), 7.95 (d, J=7.8 Hz,1H), 7.88 (d, J=7.5 Hz,1H),7.65-7.55 (m, 3H), 7.50-7.40 (m, 4H), 4.42(s, 2H), 4.33 (s, 2H), 3.80-3.40 (m, 3H), 3.10-2.95 (m, 2H), 2.50-2.35(m, 2H), 2.35-2.05 (m, 2H).

EXAMPLE 31 (12) 4-(Morpholin-4-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1833]

[1834] TLC: Rf 0.31 (ethyl acetate:methylene chloride=1:1);

[1835] NMR (CDCl₃): δ 7.69 (d, J=7.2 Hz, 1H), 7.64 (t, J=4.8 Hz, 1H),7.46 (d, J=4.8 Hz, 2H), 6.71 (d, J=7.2 Hz, 1H), 3.68 (t, J=4.5 Hz, 4H),3.60 (s, 2H), 2.44 (t, J=4.5 Hz, 4H).

EXAMPLE 32 4-Ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[1836]

[1837] To a solution of 4-Carboxy-1,1-dioxidebenzo[b]thiophene (2.42 g)in dimethylformamide (50 ml), were added potassium carbonate (3.10 g)and bromoethane (44.3 g). The mixture was stirred at room temperatureovernight. To a reaction mixture, water was added. The mixture wasextracted by ethyl acetate. The extract was washed by water and asaturated aqueous solution of sodium chloride sucessively, dried overanhydrous sodium sulfate and concentrated to give the compound of thepresent invention (2.08 g) having the following physical data.

[1838] TLC: Rf 0.24 (ethyl acetate:hexane=1:4);

[1839] NMR (CDCl₃). δ 8.25 (d, J=7.4 Hz, 1H), 8.20 (d, J=7.8 Hz, 1H),7.88 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 6.84 (d, J=7.4 Hz, 1H),4.44 (q, J=7.2 Hz, 2H), 1.44 (t, J=7.2 Hz, 3H).

EXAMPLE 32 (1) 4-Benzyloxycarbonyl-1,1-dioxidebenzo[b]thiophene

[1840]

[1841] By the same procedure as described in Example 32 using4-carboxy-1,1-dioxidebenzo[b]thiophene and benzylbromide instead ofbromoethane, the compound of the present invention having the followingphysical data was obtained.

[1842] MS (APCI, Pos.): m/z 301 (M+H)⁺.

EXAMPLE 33 4-(Pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene

[1843]

[1844] To a solution of 4-bromo-1,1-dioxidebenzo[b]thiophene (492 mg) indimethylformamide (5.0 ml), were added diethyl(3-pyridyl)boran (440 mg)and trispotassium phosphate (637 mg) andtetrakis(triphenylphosphine)palladium (0) (116 mg). The mixture wasstirred at 80° C. for 2 hours. The reaction mixture was poured intowater. The mixture was extracted by ethyl acetate. The extract waswashed by a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedwith column chromatography on silica gel (chloroform:methanol=50:1) togive the compound of the present invention (490 mg) having the followingphysical data.

[1845] TLC: Rf 0.59 (chloroform:methanol=9:1);

[1846] MS (APCI, Pos.): m/z 276 (M+MeOH+H)⁺, 244 (M+H)⁺.

EXAMPLE 33 (1) 6-(Pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene

[1847]

[1848] By the same procedure as described in Example 33, using6-bromo-1,1-dioxidebenzo[b]thiophene instead of4-bromo-1,1-dioxidebenzo[b]thiophene, and diethyl(3-pyridyl)borane, thecompound of the present invention having the following physical data wasobtained.

[1849] MS (APCI, Pos.): m/z 276 (M+MeOH+H)⁺, 244 (M+H)⁺.

EXAMPLE 344-(4,4-Dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[1850]

[1851] To the compound prepared in the following Example 72 (519 mg),was added thionyl chloride (2.1 ml). The mixture was stirred at roomtemperature for 1 hour. To the reaction mixture was added ethyl acetate.The extract was washed by a saturated aqueous solution of sodiumchloride, dried over anhydrous sodium sulfate, concentrated to give thecompound of the present invention (392 mg) having the following physicaldata.

[1852] TLC: Rf 0.42 (ethyl acetate:hexane=1:1);

[1853] NMR (CDCl₃): δ 8.43 (d, J=7.0 Hz, 1H), 8.08 (d, J=7.8 Hz, 1H),7.78 (d, J=7.8 Hz, 1H), 7.56 (t, J=7.8 Hz, 1H), 6.76 (d, J=7.0 Hz, 1H),4.13 (s, 2H), 1.40 (s, 6H).

EXAMPLES 35˜35 (68)

[1854] By the same procedure as described in Example 27, using thecompounds prepared in Examples 28˜28 (33), 29, 30˜30 (13), 31˜31 (12),32˜32 (1), 33˜33 (1), 34 or corresponding compounds instead of5-methyl-1,1-dioxidebenzo[b]thiophene, and if necessary, by convertinginto the corresponding salt by a known method, the compounds of thepresent invention having the following physical data were obtained.

EXAMPLE 35 4-(Pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1855]

[1856] Free Acid:

[1857] TLC: Rf 0.44 (methylene chloride:methanol=10:1);

[1858] NMR (DMSO-d₆): δ 9.41 (t, J=5.7 Hz, 1H), 8.67 (d, J=1.8 Hz, 1H),8.46 (dd. J=4.8, 1.8 Hz,1H), 8.06 (d, J=6.3 Hz,1H), 7.96 (d, J=6.9 Hz,1H), 7.90-7.67 (m, 5H), 7.66-7.58 (m, 2H), 7.36 (dd, J=8.1, 5.1 Hz, 1H),6.27 (d, J=6.9 Hz, 1H), 4.54 (d, J=5.7 Hz, 2H), 4.10 (dd, J=15.6, 9.3Hz, 1H), 3.98 (dd, J=15.6,1.5 Hz, 1H). hydrochloride:

[1859] TLC: Rf 0.45 (chloroform:methanol 9:1);

[1860] NMR (DMSO-d₆): δ 9.70-9.62 (br, 1H), 8.95 (s, 1H), 8.75 (d, J=5.4Hz, 1H), 8.55 (d, J=7.5 Hz, 1H), 8.13 (d, J=7.5 Hz, 1H), 7.98 (d, J=6.9Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.91-7.85 (m, 1H), 7.81-7.72 (m, 1H),7.67-7.58 (m, 4H), 6.21 (d, J=9.0 Hz, 1H), 4.76 (dd, J=15.6, 6.0 Hz,1H), 4.62 (dd, J=15.6, 5.1 Hz, 1H), 4.07 (dd, J=15.0, 9.0 Hz, 1H), 3.93(d, J=15.0Hz, 1H).

EXAMPLE 35 (1)4-(4-Benzylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[1861]

[1862] TLC: Rf 0.46 (chloroform:methanol=19:1);

[1863] NMR (DMSO-d₆): δ 11.60-11.40 and 11.40-11.20 (each br, total 1H),8.05-7.52 (m, 10H), 7.51-7.23 (m, 3H), 5.88 and 5.81 (each d, J=9.3 Hz,total 1H), 4.80-3.85 (m, 6H), 3.70-2.78 (m, 6H).

EXAMPLE 35 (2)4-(N-(2-(Pyridin-3-yl)ethyl)-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-2,2-dioxidebenzo[b]thiophene.hydrochloride

[1864]

[1865] TLC: Rf 0.27 (chloroform: methanol=19:1);

[1866] NMR (DMSO-d₆): δ 8.96 and 8.81 (each s, total 1H), 8.75 and 8.73(each d, J=5.4 Hz, total 1H), 8.55 and 8.32 (each d, J=7.5 Hz, total1H), 7.95-7.62 (m, 9H), 5.81 and 5.79 (each d, J=8.4 Hz, total 1H),4.15-3.84 and 3.73-3.62 (each m, total 4H), 3.50-3.05 (m, 2H), 3.16 and3.13 (each s, total 3H).

EXAMPLE 35 (3)4-(2-(2-Hydroxyethoxy)ethyl)carbamoyl-3-phenylSulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1867]

[1868] TLC: Rf 0.55 (methylene chloride:methanol=9:1);

[1869] NMR (DMSO-d₆): δ 8.84 (t, J=5.4 Hz, 1H), 7.98-7.90 (m, 2H), 7.84(d, J=7.5 Hz, 1H), 7.81-7.73 (m, 3H), 7.69-7.60 (m, 2H), 6.36 (d, J=8.9Hz, 1H), 4.58 t, J=5.1 Hz, 1H), 4.09 (dd, J=15.3, 8.9 Hz, 1H), 3.9 6 (d,J=15.3 Hz, 1H), 3.67-3.53 (m, 2H), 3.53-3.35 (m, 6H).

EXAMPLE 35 (4)4-(2,4-Dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1870]

[1871] TLC: Rf 0.48 (methylene chloride:methanol=95:5);

[1872] NMR (DMSO-d₆): δ 5 9.04 (t, J=5 Hz, 1H), 8.03 (d, J=7.2 Hz, 1H),7.92 (d, J=7.2 Hz, 1H), 7.90-7.70 (m, 5H), 7.62 (t, J=7.2 Hz, 1H), 7.32(d, J=8.4 Hz, 1H), 6.57 (d, J=2.4 Hz, 1H), 6.47 (dd , J=8.4, 2.4 Hz,1H), 6.27 (d, J=8.5 Hz, 1H), 4.47 (dd, J=15, 5 Hz, 1H), 4.29 (dd, J=15,5Hz, 1H), 4.08 (dd, J=15, 8.5 Hz, 1H), 3.97 (d, J=15 Hz, 1H), 3.83 (s,3H), 3.74 (s, 3H).

EXAMPLE 35 (5) 4-(1-Benzylpiperidin-4-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1873]

[1874] Free Compound:

[1875] TLC: Rf 0.30 (methylene chloride:methanol=9:1);

[1876] NMR (CDCl₃+CD₃OD). δ 8.00-7.50 (m, 8H), 7.45-7.20 (m, 1H), 6.25(dd, J=7.5, 2.5 Hz, 1H), 4.10-3.90 (m, 1H), 3.8 0 (dd, J=15, 2.5 Hz, H),3.70-3.60 (m, H), 3.55 (s, 2H), 3.10-2.90 (m H, ), 2.30-1.95 (m, 4H),1.90-1.70 (m, 2H).

[1877] Hydrochloride:

[1878] TLC: Rf 0.40 (methanol:ethyl acetate=1:10);

[1879] NMR (CD₃OD): δ 8.04-7.43 (m, 13H), 6.15 (dd, J=8.2 Hz, 2.6 Hz,1H), 4.35 (s, 2H), 4.34-4.06 (m,1H), 3.94 (dd, J=15.2 Hz, 8.2 Hz,1H),3.83 (dd, J=15.2 Hz, 2.6 Hz,1H), 3.74-3.08 (m, 4H), 2.56-1.56 (m, 4H).

[1880] Methanesulfonic Acid Salt:

[1881] TLC: Rf 0.40 (methanol:ethyl acetate=1:10);

[1882] NMR (CD₃OD): δ 8.06-7.44 (m, 13H), 6.14 (dd, J=8.2 Hz, 2.6 Hz,1H), 4.34 (s, 2H), 4.32-4.12 (m,1H), 4.01-3.77 (m, 2H), 3.68-3.08 (m,4H), 2.69 (s, 3H), 2.54-1.74 (m, 4H).

EXAMPLE 35 (6)4-(Pyridin-4-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1883]

[1884] TLC: Rf 0.35 (chloroform:methanol=9:1);

[1885] NMR (DMSO-d₆). δ 9.45 (t. J=7 Hz, 1H), 8.50 (d, J=8 Hz, 2H), 8.10(d, J=8 Hz, 1H), 8.00 (d, J=8 Hz, 1H), 7.90 (t, J=8 Hz,1H), 7.80-7.55(m, 5H), 7.45 (d, J=8 Hz, 2H), 6.30 (dd, J=1 Hz and 7 Hz, 1H), 4.55 (m,2H), 4.10 (dd, J=7 Hz and 15 Hz, 1H), 4.00 (dd, J=1 Hz and 15 Hz, 1H).

EXAMPLE 35 (7)4-(2-t-Butoxycarbonylethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1886]

[1887] TLC: Rf 0.37 (ethyl acetate:hexane=3:2);

[1888] NMR (DMSO-d₆): δ 8.90 (t, J=7 Hz, 1H), 8.00-7.55 (m, 8H), 6.25(dd, J=1 Hz and 7Hz, 1H), 4.10 (dd, J=7Hz and 15Hz, 1H), 3.95 (dd, J=1Hz and 15 Hz, 1H), 3.45 (m, 2H), 2.60 (t, J=7 Hz, 2H).

EXAMPLE 35 (8)4-(Thiophen-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1889]

[1890] TLC: Rf 0.67 (chloroform:methanol=4:1);

[1891] NMR (DMSO-d₆): δ 9.40 (t, J=7 Hz, 1H), 8.00-7.60 (m, 8H), 7.40(d, J=6 Hz, 1H), 7.10 (d, J=4 Hz, 1H), 7.00 (dd, J=4 Hz and6 Hz, 1H),6.30 (dd, J=1 Hz and7 Hz, 1H), 4.75 (dd, J=7 Hz and 16 Hz, 1H), 4.55(dd, J=7 Hz and 16 Hz, 1H),4.10 (dd, J=7 Hz and 12 Hz, 1H), 4.00 (dd,J=1 Hz and 12 Hz, 1H).

EXAMPLE 35 (9)4-Benzylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1892]

[1893] TLC: Rf 0.58 (methylene chloride:methanol=10:1);

[1894] NMR (CDCl₃+DMSO-d₆): δ 8.74 (t, J=5.7 Hz,1H), 8.03 (dd, J=7.8,0.9 Hz, 1H), 7.93-7.80 (m, 3H), 7.78-7.68 (m, 2H), 7.59 (t, J=7.8 Hz,2H), 7.50 (d, J=6.9 Hz, 2H), 7.39-7.20 (m, 3H), 6.36 (d, J=7.8 Hz, 1H),4.71 (dd, J=14.9, 5.7 Hz, 1H), 4.62 (dd, J 14.9, 5.7 Hz, 1H), 3.86 (d,J=15.0 Hz, 1H), 3.69 (dd, J=15.0, 7.8 Hz, 1H).

EXAMPLE 35 (10)4-(Pyridin-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1895]

[1896] TLC: Rf 0.56 (methylene chloride:methanol=10:1);

[1897] NMR (DMSO-d₆): δ 9.42 (t, J=6.3 Hz, 1H), 8.54 (d, J=5.1 Hz, 1H),8.11 (d, J=7.5 Hz, 1H), 7.97 (d, J=8.1 Hz, 1H), 7.95-7.82 (m, 1H),7.80-7.70 (m, 4H). 7.62 (t, J=8.1 Hz, 2H), 7.55 (d, J=8.1 Hz, 1H),7.30-7.24 (m, 1H), 6.30 (d, J=8.7 Hz, 1H), 4.65 (dd, J=16.0,4.8 Hz, 1H),4.54 (dd, J=16.0, 4.8 Hz, 1H), 4.10 (dd, J=15.6,4.8 Hz, 1H), 4.00 (d,J=15.6, 9.3 Hz, 1H).

EXAMPLE 35 (11) 4-(2-(Piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1898]

[1899] Free Compound:

[1900] TLC: Rf 0.10 (methylene chloride:methanol=10:1);

[1901] NMR (CDCl₃): δ 7.90-7.78 (m, 4H), 7.75-7.64 (m, 2H), 7.62-7.51(m, 2H), 7.42 (bs, 1H), 6.29 (d, J=8.1 Hz, 1H), 3.84 (dd, J=15.0, 1.5Hz, 1H), 3.75-3.60 (m, 2H), 3.58-3.45 (m, 1H), 2.77-2.60 (m , 2H),2.55-2.40 (m, 4H), 1.80-1.40 (m, 6H).

[1902] Hydrochloride:

[1903] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[1904] NMR (DMSO-d₆): δ 10.25 (br. s, 1H), 9.32 (t, J=5.4 Hz, 1H),8.10(dd, J=7, 1.4 Hz, 1H), 8.00-7.80 (m, 2H),7.80-7.70 (m, 3H), 7.70-7.55(m, 2H),6.30 (d, J=8 Hz, 1H), 4.14 (dd, J=15, 8 Hz, 1H ), 3.97 (d, J=15Hz, 1H), 3.90-3.70 (m, 2H),3.70-3.50 (m, 2H), 3.50-3.10 (m, 3H),3.10-2.80(m, 2H), 2.00-1.60 (m, 4H), 1.60-1.20 (m, 1H).

[1905] Methanesulfonic Acid Salt:

[1906] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[1907] NMR (DMSO-d₆): δ 9.13 (t, J=5 Hz, 1H), 9.00 (br. s, 1H), 8.05(dd, J=7, 1.4 Hz, 1H), 8.00-7.80 (m, 2H), 7.80-7.70 (m, 3H), 7.70-7.55(m, 2H), 6.28 (d, J=8.2 Hz, 1H), 4.12 (dd, J=16, 8.2 Hz, 1H), 3.94 (d,J=16 Hz, 1H), 3.90-3.50 (m, 5H), 3.50-3.20 (m, 2H), 3.15-2.90 (m, 2H),2.00-1.60 (m, 4H), 1.60-1.30 (m, 1H).

EXAMPLE 35 (12a)4-((1S)-1-t-Butoxycarbonyl-2-methylpropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1908]

[1909] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[1910] NMR (CDCl₃): δ 7.99 (dd, J=7.5, 0.9 Hz, 1H), 7.87-7.84 (m, 3H),7.75 (t, J=7.5 Hz, 1H), 7.72-7.67 (m, 1H), 7.60-7.55 (m, 2H), 6.80 (d,J=8.8 Hz, 1H), 6.25 (d, J=8.7 Hz, 1H), 4.67 (dd, J=8.8, 3.9 Hz, 1H),3.80 (d-like, J=15.0 Hz, 1H), 3.65 (dd, J=15.0, 8.7 Hz, 1H), 2.47-2.41(m, 1H), 1.54 (s, 9H), 1.12 (d, J=7.0 Hz, 3H), 1.06 (d, J=7.0 Hz, 3H).

[1911] (The determination of the absolute configuration of the carbonatom to which phenylsulfonyl is bonded is not performed, but thiscompound is a single isolated one.)

EXAMPLE 35 (12b) 4-((1S)-1-t-Butoxycarbonyl-2-methypropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1912]

[1913] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[1914] NMR (CDCl₃): δ 7.98 (d, J=7.8 Hz, 0.5H), 7.91-7.80 (m, 3.5H),7.76-7.67 (m, 2H), 7.60-7.55 (m, 2H), 6.92 (d, J=8.1 Hz, 0.5H), 6.84 (d,J=8.7 Hz, 0.5H), 6.25 (dd, J=9.3, 1.5 Hz, 0.5H), 6.18 (dd, J=9.3, 1.5Hz, 0.5H), 4.66 (dd, J=8.7, 3.9 Hz, 0.5H), 4.62 (dd, J=8.1, 5.3 Hz,0.5H), 3.87 (dd, J=15.0, 1.5 Hz, 0.5H), 3.80 (dd, J=15.0, 1.5 Hz, 0.5H),3.67 (dd, J=15.0, 9.3 Hz, O.SH), 2.41-2.36 (m, 0.5H), 2.33-2.24 (m,0.5H), 1.54 (s, 4.5H), 1.46 (s, 4.5H), 1.11 (d, J=6.9 Hz, 1.5H), 1.07(d, J=6.9 Hz, 1.5H), 1.06 (d, J=6.9 Hz, 1.5H), 1.05 (d, J=6.9 Hz, 1.5H).

EXAMPLE 35 (13)4-(2-Fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1915]

[1916] TLC: Rf 0.60 (chloroform:methanol=9:1);

[1917] NMR (DMSO-d₆): δ 9.35 (t, J=7Hz, 1H), 8.05 (d, J=8Hz, 1H), 7.95(d, J=8Hz, 1H), 7.85 (t, J=8 Hz, 1H), 7.80-7.50 (m, 6H), 7.40-7.10 (m,3H), 6.25 (d, J=10 Hz, 1H), 4.60 (dd, J=16 Hz and 7Hz, 1H),4.45 (dd,J=16 Hz and 7Hz, 1H),4.10 (dd, J=16Hz and 10 Hz, 1H), 4.00 (d, J=16 Hz,1H).

EXAMPLE 35 (14)4-(3-Fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1918]

[1919] TLC: Rf 0.60 (chloroform:methanol=9:1);

[1920] NMR (DMSO-d₆): δ 9.40 (t, J=7 Hz, 1H), 8.05 (d, J=8 Hz, 1H), 7.95(d, J=8 Hz, 1H), 7.85 (t, J=8 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m,2H), 7.45-7.20 (m, 3H), 7.05 (m, 1H), 6.25 (d, J=10 Hz, 1H), 4.55 (d,J=7 Hz, 2H), 4.10 (dd, J=16 Hz and 10 Hz, 1H), 3.97 (dd, J=16 Hz, 1H).

EXAMPLE 35 (15)4-(3-Methylphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1921]

[1922] TLC: Rf 0.69 (chloroform:methanol=9:1);

[1923] NMR (DMSO-d₆): δ 9.31 (t, J=6.0 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H),7.96 (d, J=7.6 Hz, 1H), 7.85 (t, J=7.6 Hz, 1H), 7.80-7.70 (m, 3H),7.70-7.55 (m, 2H), 7.30-7.15 (m, 3H), 7.15-7.00 (m, 1H), 6.31 (dd, J=8.6Hz and 2.0 Hz, 1H), 4.48 (m, 2H), 4.10 (dd, J=15 Hz and 8.6 Hz, 1H),3.98 (dd, J=15 Hz and 2.0 Hz, 1H), 2.27 (s, 3H).

EXAMPLE 35 (16)4-(2-Methoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1924]

[1925] TLC: Rf 0.70 (chloroform:methanol=9:1);

[1926] NMR (DMSO-d₆): δ 9.15 (t-like, J=6 Hz, 1H), 8.08 (d, J=7.5 Hz,1H), 7.95 (d, J 7.5 Hz,1H), 7.85 (t, J=7.5 Hz,1H), 7.80-7.70 (m, 3H),7.70-7.55 (m, 2H), 7.50-7-35 (m, 1H), 7.35-7.20 (m, 1H), 7.10-6.80 (m,2H), 6.28 (d, J=8 Hz, 1H), 4.57 (dd, J=16 Hz and 6 Hz, 1H), 4.35 (dd,J=16 Hz and 6 Hz, 1H), 4.10 (dd, J=15.5 Hz and 8 Hz, 1H), 4.00 (d,J=15.5 Hz, 1H), 3.85 (s, 3H).

EXAMPLE 35 (17)4-(2,3-Dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1927]

[1928] TLC: Rf 0.52 (chloroform:methanol=9:1);

[1929] NMR (DMSO-d₆): δ 9.22 (t, J=5.5 Hz, 1H), 8.05 (d, J=7.0 Hz, 1H),7.95 (d, J=7.0 Hz, 1H), 7.85 (t, J=7.0 Hz, 1H), 7.80-7.70 (m, 3H),7.70-7.57 (m, 2H), 7.15-6.90 (m, 3H), 6.29 (dd, J=8.5 Hz and 2.0 Hz,1H), 4.62 (dd, J=15.0 Hz and 5.5 Hz, 1H), 4.38 (dd, J=15.0 Hz and 5.5Hz, 1H), 4.11 (dd, J=15.5 Hz and 8.5 Hz, 1H), 3.99 (dd, J=15.5 Hz and2.0 Hz, 1H), 3.82 (s, 6H).

EXAMPLE 35 (18)4-(3,4-Dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1930]

[1931] TLC: Rf 0.48 (chloroform:methanol=9:1);

[1932] NMR (DMSO-d₆): δ 9.27 (t, J=6.0 Hz, 1H), 8.04 (d, J=7.5 Hz, 1H),7.95 (d, J=7.5 Hz, 1H), 7.85 (t, J=7.5 Hz, 1H), 7.80-7.70 (m, 3H),7.70-7.57 (m, 2H), 7.44 (s, 1H), 7.00-6.85 (m, 2H), 6.31 (dd, J=8.6 Hzand 1.4 Hz, 1H), 4.45 (m, 2H), 4.11 (dd, J=15.0 Hz and 8.6 Hz, 1H), 3.99(dd, J=15.0 Hz and 1.4 Hz, 1H), 3.73 (s, 3H), 3.72 (s, 3H).

EXAMPLE 35(19)4-(2,5-Difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1933]

[1934] TLC: Rf 0.59 (chloroform:methanol=9:1);

[1935] NMR (DMSO-d₆): δ 9.41 (t, J=5.8Hz, 1H), 8.09 (dd, J=7.6Hz and 1.5Hz, 1H), 7.98 (dd, J=7.6 Hz and 1.5 Hz, 1H), 7.87 (t, J=7.6 Hz,1H),7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.50-7.35 (m, 1H), 7.35-7.07 (m,2H), 6.26 (dd, J=15 Hz and 8.4 Hz,1H), 4.54 (d, J=5.8 Hz, 2H), 4.10 (dd,J=15 Hz and 8.4 Hz, 1H), 3.97 (dd, J=15 Hz and 2.0 Hz,1H).

EXAMPLE 35 (20)4-(3,4,5-Trimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1—dioxidebenzo[b]thiophene

[1936]

[1937] TLC: Rf 0.58 (chloroform:methanol=9:1);

[1938] NMR (DMSO-d₆): δ 9.31 (m, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.95 (d,J=7.6 Hz, 1H), 7.85 (t, J=7.6 Hz, 1H),7.80-7.70 (m, 3H), 7.70-7.55 (m,2H), 6.79 (s, 2H), 6.32 (d, J=8.4 Hz, 1H), 4.61 (dd, J=15.2 Hz and 6.6Hz, 1H), 4.37 (dd, J=15.2 Hz and 4.6 Hz, 1H), 4.12 (dd, J=15 Hz and 8.4Hz, 1H), 3.99(d, J=15 Hz, 1H), 3.73 (s, 6H), 3.61 (s, 3H).

EXAMPLE 35 (21)4-(Benzimidazol-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1939]

[1940] TLC: Rf 0.27 (chloroform:methanol=9:1);

[1941] NMR (DMSO-d₆): δ 12.23 (broad-s, 1H), 9.48 (m, 1H), 8.17 (d, J=7Hz, 1H), 8.00-7.80 (m, 2H), 7.80-7.70 (m, 3H), 7.70-7.45 (m, 4H),7.20-7.10 (m, 2H), 6.29 (d, J=8 Hz, 1H), 4.89 (dd, J=16 Hz and 6 Hz,1H), 4.51 (dd, J=16 Hz and 5 Hz, 1H), 4.13 (dd, J=15 Hz and 8 Hz, 1H),3.99 (d, J=15 Hz, 1H).

EXAMPLE 35 (22)4-(3,5-Difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1942]

[1943] TLC: Rf 0.63 (chloroform:methanol=9:1);

[1944] NMR (DMSO-d₆): δ 9.44 (t, J=5.6 Hz, 1H), 8.11 (d, J=7.4 Hz, 1H),7.98 (d, J=7.4 Hz,1H), 7.88 (t, J=7.4 Hz,1H), 7.80-7.70 (m, 3H),7.70-7.55 (m, 2H), 7.30-7.00 (m, 3H), 6.29 (dd, J=8.5 Hz and 2 Hz, 1H),4.55 (m, 2H), 4.11 (dd, J=15 Hz and 8.5 Hz, 1H), 3.98 (dd, J=15 Hz and 2Hz,1H).

EXAMPLE 35 (23)4-(N-Benzyl-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1945]

[1946] NMR (CDCl₃): δ 8.00-7.25 (m, 13H), 6.00-5.90 (m, 1H), 5.19 (d,J=15 Hz) and 5.03 (d, J=18 Hz, total 1H), 4.49 (d, J=15 Hz) and 4.40 (d,J=18 Hz, total 1H), 3.75 (dd, J=2 Hz and 15 Hz, 1H), 3.63 (dd, J=8.5 Hzand 15 Hz, 1H), 3.18 and 3.12 (each s, total 3H).

EXAMPLE 35 (24)4-(4-Nitrophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1947]

[1948] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1949] NMR (DMSO-d₆): δ 9.52 (m, 1H), 8.30-7.55 (m, 13H), 6.27 (d, J=6.4Hz, 1H), 4.65 (m, 2H), 4.10 (dd, J=15.5 Hz and 6.4 Hz, 1H), 3.97 (d,J=15.5 Hz, 1H).

EXAMPLE 35 (25)5-(2-Hydroxyethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1950]

[1951] TLC: Rf 0.39 (ethyl acetate:methanol=95:5);

[1952] NMR (DMSO-d₆): δ 8.79 (t, J=5.7 Hz, 1H), 8.18 (brs,1H), 8.14 (d,J=8.1 Hz,1H), 7.91 (d, J=8.1 Hz,1H), 7.82-7.75 (m, 3H), 7.68-7.58 (m,2H), 5.83 (dd, J=9.4 Hz, 8.0 Hz, 1H), 4.77 (t, J=5.7 Hz, 1H), 4.03 (dd,J=15.0 Hz, 9.6 Hz, 1H), 3.84 (dd, J=15.0 Hz, 3.0 Hz, 1H), 3.54 (q, J=5.7Hz, 2H), 3.36 (q, J=5.7 Hz, 2H).

EXAMPLE 35 (26)5-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1953]

[1954] Free Compound:

[1955] TLC: Rf 0.32 (ethyl acetate:methanol=9:1);

[1956] NMR (CDCl₃): δ 8.59-8.56 (m, 2H), 8.04 (d, J=8.5 Hz, 1H),7.74-7.68 (m, 3H), 7.58-7.53 (m, 1H), 7.47-7.31 (m, 5H), 5.16 (d, J=8.5Hz, 1H), 4.68 (dd, J=15.0, 6.0 Hz, 1H), 4.59 (dd, J=15.0, 6.0 Hz, 1H),4.11 (d, J=15.0 Hz, 1H), 3.77 (dd, J=15.0, 8.5 Hz, 1H), 3.67 (s, 3H).

[1957] Hydrochloride:

[1958] TLC: Rf 0.32 (ethyl acetate:methanol=9:1);

[1959] NMR (DMSO-d₆): δ 9.37 (t, J=5.5 Hz, 1H), 8.90 (s, 1H), 8.84 (d,J=5.5 Hz, 1H), 8.49 (d, J=8.0 Hz, 1H), 8.02 (dd, J=8.0, 5.5 Hz, 1H),7.85-7.75 (m, 4H), 7.67-7.56 (m, 3H), 5.70 (d, J=9.0 Hz, 1H), 4.72-4.60(m, 2H), 4.15 (d, J=15.0 Hz, 1H), 4.02 (dd, J=15.0, 9.0 Hz, 1H), 3.56(s, 3H).

EXAMPLE 35 (27)5-(2-Dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1960]

[1961] Free Compound:

[1962] TLC: Rf 0.24 (ethyl acetate:methanol:triethylamine=8:1:1);

[1963] NMR (CDCl₃): δ 8.00 (d, J=8.0 Hz, 1H), 7.76-7.73 (m, 2H),7.67-7.61 (m, 1H), 7.51-7.41 (m, 3H), 7.32 (bt, J=5.0 Hz, 1H), 5.23 (t,J=9.0 Hz, 1H), 4.19 (d, J=15.0 Hz, 1H), 3.81 (dd, J=15.0, 9.0 Hz, 1H),3.77 (s, 3H), 3.64-3.42 (m, 2H), 2.51 (t, J=6.0 Hz, 1H), 2.28 (s, 6H).

[1964] Hydrochloride:

[1965] TLC: Rf 0.24 (ethyl acetate:methanol:triethylamine=8:1:1);

[1966] NMR (DMSO-d₆): δ 10.47 (br, 1H), 8.90 (t, J=5.5 Hz, 1H),7.86-7.76 (m, 4H), 7.69-7.64 (m, 2H), 7.56 (d, J=8.0 Hz, 1H), 5.69 (d,J=8.5 Hz, 1H), 4.13 (d, J=15.0 Hz, 1H), 4.00 (d, J=15.0, 8.5 Hz, 1H),3.65-3.60 (m, 2H), 3.63 (s, 3H), 3.25 (t, J=6.0 Hz, 2H), 2.82 (s, 6H).

EXAMPLE 35 (28)5-Dimethylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1967]

[1968] TLC: Rf 0.35 (ethyl acetate);

[1969] NMR (DMSO-d₆): δ 7.83 (d, J=8.0 Hz, 2H), 7.44 (t, J=7.5 Hz, 1H),7.63 (dd, J=8.0 Hz, 7.5 Hz, 2H), 7.49 (d, J=8.0 Hz,1H), 7.46 (d, J=7.5Hz,1H), 5.63 (d, J=8.5 Hz, 1H), 4.13 (d, J=14.5 Hz, 1H), 4.02 (dd,J=14.5 Hz, 8.5 Hz, 1H), 3.59 (s, 3H), 3.01 (s, 3H), 2.78 (s, 3H).

EXAMPLE 35 (29)5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1970]

[1971] TLC: Rf 0.21 (ethyl acetate:hexane=2:1);

[1972] NMR (DMSO-d₆): δ 7.87-7.70 (m, 3H), 7.70-7.60 (m, 2H), 7.60-7.53(m, 2H),5.67 (d, J=8.7 Hz, 1H), 4.26 (d, J=15.0 Hz, 1H), 4.05 (dd,J=15.0, 8.7 Hz, 1H), 3.70-3.54 (m, 2H), 3.48 (s, 3H), 3.20-3.15 (m,2H),1.85-1.40 (m, 8H).

EXAMPLE 35 (30)5-(2,3-Dihydroindol-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1973]

[1974] TLC: Rf 0.54 (ethyl acetate:hexane=2:1);

[1975] NMR (DMSO-d₆): δ 8.13 (d, J=7.8 Hz, 1H), 7.87 (d, J=7.5 Hz, 1H),7.83-7.70 (m, 2H), 7.70-7.56 (m, 2H), 7.66 (t, J=7.8 Hz, 2H), 7.31 (d,J=7.5 Hz,1H), 7.25 (t, J=7.5 Hz, 1H), 7.12 (t, J=7.5 Hz, 1H), 5.72 (d,J=8.7 Hz, 1H), 4.39-3.97 (m, 2H), 3.76 (dd, J=18.6, 8.7 Hz, 1H),3.70-3.50 (m, 1H), 3.57 (s, 3H), 3.21-3.08 (m, 2H).

EXAMPLE 35 (31)5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1976]

[1977] TLC: Rf 0.78 (methylene chloride:methanol=10:1);

[1978] NMR (CDCl₃+DMSO-d₆): δ 7.94-7.86 (m, 1H), 7.77-7.66 (m, 2H),7.64-7.50 (m, 4H), 7.44-7.16 (m, 2H), 7.10699 (m, 2H),5.38-5.27 (m, 1H),4.26-4.00 (m, 2H), 3.95 and 3.78 (each s, total 3H), 3.90-3.65 (m,2H),3.50-2.80 (m, 6H).

EXAMPLE 35 (32)5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1979]

[1980] TLC: Rf 0.51 (methylene chloride:methanol=10:1);

[1981] NMR (CDCl₃): δ 7.93-7.86 (m, 1H), 7.74-7.43 (m, 7H), 7.40-7.30(m, 3H), 5.31-5.20 (m, 1H), 4.24-3.64 (m, 7H), 3.34-3.10 (m, 2H),3.06-2.90 (m, 2H), 2.70-2.30 (m, 6H).

EXAMPLE 35 (33)4-(Pyridin-3-ylcarbonyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1982]

[1983] Free Compound:

[1984] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[1985] NMR (DMSO-d₆): δ 9.31 (t, J=6.0 Hz, 1H), 9.05 (d, J=1.5 Hz, 1H),8.72 (dd, J 5.0, 1.5 Hz, 1H), 8.23 (dt, J=8.0, 1.5 Hz. 1H); 7.87-7.63(m, 8H), 7.52 (dd, J=8.0, 5.0 Hz, 1H), 6.05 (d, J=8.5 Hz, 1H), 5.01 (dd,J=16.0, 6.0 Hz, 1H), 4.78 (dd, J=16.0, 6.0 Hz, 1H), 4.02 (dd, J=15.3,8.5 Hz, 1H), 3.86 (d, J=15.3 Hz, 1H).

[1986] Hydrochloride:

[1987] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[1988] NMR (DMSO-d₆): δ 9.63-9.59 (m, 1H), 9.20 (s, 1H), 8.86 (d, J=5.0Hz, 1H), 8.57-8.54 (m, 1H), 7.87-7.63 (m, 9H), 6.11 (d, J=8.5 Hz, 1H),5.02 (dd, J=15.8, 5.7 Hz, 1H), -4.80 (dd, J=15.8, 5.7 Hz, 1H), 4.00 (dd,J=15.5, 8.5 Hz, 1H), 3.86 (d, J=15.5 Hz, 1H).

EXAMPLE 35 (34)4-(3-Pyrrol-1-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1989]

[1990] TLC: Rf 0.20 (ethyl acetate:hexane=1:1);

[1991] NMR (CDCl₃): δ 7.75-7.35 (m, 6H), 7.24 (d, J=8 Hz, 1H), 6.93 (d,J=8 Hz, 1H), 6.68 (t, J=2 Hz, 2H), 6.15 (t, J=2 Hz, 2H), 5.21 (d, J=9Hz, 1H), 4.53-4.00 (m, 2H), 4.10 (d, J=15 Hz, 1H), 4.00-3.65 (m, 2H),3.73 (dd, J=9, 15 Hz, 1H), 2.19 (quint, J=5 Hz, 2H).

EXAMPLE 35 (35)4-(Quinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1992]

[1993] Free Compound:

[1994] TLC: Rf 0.21 (benzene:ethyl acetate=2:1);

[1995] NMR (CDCl₃): δ 8.42 (d, J=9 Hz, 1H), 8.03 (d, J=8 Hz, 2H),7.90-7.20 (m, 11H), 5.80 (d, J=8 Hz, 1H), 5.31 (d, J=13 Hz, 1H), 5.09(d, J=13 Hz, 1H), 4.24 (d, J=15 Hz, 1H), 4.02 (dd, J=8, 15 Hz, 1H).hydrochloride:

[1996] TLC: Rf 0.30 (hexane:ethyl acetate=1:2);

[1997] NMR (DMSO-d₆): δ 8.64 (d, J=8.5 Hz, 1H), 8.20 (d, J=8.5 Hz, 1H),8.13 (d, J=8.5 Hz, 1H), 7.92 (t-like, J=8.5 Hz, 1H), 7.81-7.65 (m, 5H),7.48-7.31 (m, 5H), 5.91 (d, J=9.0 Hz, 1H), 5.42 (d, J=13.5 Hz, 1H), 5.21(d, J=13.5 Hz, 1H), 4.22 (d, J=15.0 Hz, 1H), 4.02 (dd, J=9.0 Hz, 1H).

EXAMPLE 35 (36)4-(2-(Pyrrol-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1998]

[1999] TLC: Rf 0.36 (hexane:ethyl acetate=1:2);

[2000] NMR (CDCl₃+CD₃OD): δ 7.85-7.58 (m, 3H), 7.58-7.42 (m, 3H), 7.28(d, J=8 Hz, 1H), 6.92 (d, J=8 Hz, 1H), 6.74 (t, J=2 Hz, 2H), 6.18 (t,J=2 Hz, 2H), 5.16 (d, J=9 Hz, 1H), 4.30-4.05 (m, 5H), 3.73 (dd, J=9,15Hz, 1H).

EXAMPLE 35 (37)4-(2-(4-Methylthiazol-5-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2001]

[2002] TLC: Rf 0.25 (ethyl acetate);

[2003] NMR (CD₃OD): δ 9.88 (s, 1H), 7.80-7.40 (m, 6H), 7.26 (d, J=8 Hz,1H), 7.25 (d, J=8Hz, 1H), 5.48 (d, J=9 Hz, 1H), 4.42-4.18 (m, 2H), 4.08(d, J=15 Hz, 1H), 3.92 (dd, J=9,15 Hz, 1H), 3. 55-3.15 (m, 2H), 2.60 (s,3H).

EXAMPLE 35 (38)4-(3-(Pyridin-4-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2004]

Free Compound:

[2005] TLC: Rf 0.26 (ethyl acetate:methanol=10:1);

[2006] NMR (CDCl₃): δ 8.53 (dd, J=1, 5 Hz, 2H), 7.78-7.35 (m. 6H), 7.25(d, J=7 Hz, 1H), 7.17 (d, J=6 Hz, 2H), 6.95 (d, J=8 Hz, 1H), 5.17 (d,J=9 Hz, 1H), 4.14 (d, J=15 Hz, IH), 4.05-3.82 (m , 2H), 3.74 (dd, J=9,15 Hz, 1H), 2.87 (t, J=6 Hz, 2H), 2.10 (quint, J=6 Hz, 2H).

[2007] Hydrochloride:

[2008] TLC: Rf 0.39 (ethyl acetate:methanol:ammonia water=100:10:1);

[2009] NMR (DMSO-d₆): δ 8.83 (d, J=6 Hz, 2H), 7.90 (d, J=5 Hz, 2H),7.85-7.52 (m, 6H), 7.34 (d, J=8 Hz, 1H), 7.24 (d, J=8 Hz, 1H), 5.64 (d,J=9 Hz, 1H), 4.18 (d, J=15 Hz, 1H), 4.00 (dd, J=9,15 Hz, 1H), 3.10-2.80(m, 2H), 2.10-1.60 (m, 2H).

EXAMPLE 35 (39)4-(1-t-Butoxycarbonylpiperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2010]

[2011] TLC: Rf 0.23 (hexane:ethyl acetate=1:1);

[2012] NMR (CD₃OD): δ 7.95-7.45 (m, 6H), 7.40-7.05 (m, 2H), 5.53 (d, J=9Hz, 1H), 4.15 (d, J=15 Hz, 1H), 3.92 (dd, J=9,15 Hz, 1H), 4.05-3.55 (m,4H), 3.20-2.40 (m, 2H), 2.00-1.20 (m, 5H), 1.47 and 1.44 (each s, 9H).

EXAMPLE 35 (40)4-(2-(Pyrrolidin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2013]

Free Compound:

[2014] TLC: Rf 0.17 (chloroform:methanol=10:1);

[2015] NMR (CDCl₃): δ 7.85-7.68 (m, 2H), 7.68-7.35 (m, 4H), 7.28 (d, J=8Hz, 1H), 6.97 (d, J=8 Hz, 1H), 5.30 (d, J=9 Hz, 1H), 4.23 (d, J=15 Hz,1H), 4.15-3.95 (m, 1H), 3.95-3.70 (m, 1H), 3.74 (dd, J=9, 15 Hz,1H),2.78 (t, J=6 Hz, 2H), 2.70-2.45 (m, 4H), 1.95-1.60 (m, 4H).

[2016] Hydrochloride:

[2017] TLC: Rf 0.36 (ethyl acetate:acetic acid:water=3:1:1);

[2018] NMR (CDCl₃+CD₃OD): δ 7.98-7.82 (m,2H), 7.80-7.45 (m, 4H), 7.34(d, J=8 Hz, 1H), 7.26 (d, J=8 Hz, 1H), 6.20-6.05 (m, 1H), 4.75-4.50 (m,1H), 4.50-4.25 (m, 1H), 4.10-3.85 (m, 2H), 3.85-3.45 (m, 4H), 3.30-2.90(m, 2H), 2.40-2.00 (m, 4H).

EXAMPLE 35 (41) 4-(2-(Piperidin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2019]

[2020] Free Compound:

[2021] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2022] NMR (CDCl₃): δ 7.85-7.67 (m, 2H), 7.67-7.36 (m, 4H), 7.27 (d, J=8Hz, 1H), 6.97 (d, J=8 Hz, 1H), 5.29 (d, J=9 Hz, 1H), 4.25 (d, J=15 Hz,1H), 4.18-3.92 (m, 1H), 3.92-3.65 (m, 1H), 3.74 (dd, J=9, 15 Hz, 1H),2.62 (t, J=6 Hz, 2H), 2.46 (t, J=6 Hz, 4H), 1.90-1.35 (m, 6H).

[2023] Hydrochloride:

[2024] TLC: Rf 0.40 (ethyl acetate:acetic acid:water=3:1:1);

[2025] NMR (CDCl₃+CD₃OD): δ 7.95-7.75 (m, 2H), 7.75-7.45 (m, 4H), 7.32(d, J=8 Hz, 1H), 7.30 (d, J=8 Hz, 1H), 6.05-5.85 (m, 1H), 4.75-4.38(m,2H), 3.95-3.42 (m, 6H), 3.15-2.85 (m, 2H), 2.35-1.35 (m, 6H).

EXAMPLE 35 (42)4-(2-(2-Acetyloxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2026]

[2027] TLC: Rf 0.17 (ethyl acetate:hexane=2:1);

[2028] NMR (CDCl₃): δ 7.82-7.70 (m, 2H), 7.65-7.35 (m, 4H), 7.27 (d, J=8Hz, 1H), 7.00 (d, J=8 Hz, 1H), 5.30 (d, J=9 Hz, 1H), 4.32-4.05 (m, 4H),4.05-3.88 (m, 1H), 3.84-3.75 (m, 5H), 2.05 (s, 3H).

EXAMPLE 35 (43)4-(2-(4-Benzylpiperazin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2029]

[2030] Free Compound:

[2031] TLC: Rf 0.42 (chloroform:methanol=5:1);

[2032] NMR (CDCl₃): δ 7.80-7.68 (m, 2H), 7.68-7.37 (m, 4H), 7.37-7.18(m, 6H), 6.96 (d, J=8 Hz, 1H), 5.27 (d, J=9 Hz, 1H), 4.22 (d, J=15 Hz,1H), 4.15-3.94 (m, 1H), 3.94-3.70 (m, 1H), 3.72 (dd , J=9, 15 Hz, 1H),3.52 (s, 2H), 2.68 (t, J=6 Hz, 2H), 2.63-2.35 (m, 8H).

[2033] 2hydrochloride:

[2034] TLC: Rf 0.28 (ethyl acetate:acetic acid:water=3:1:1);

[2035] NMR (CD₃OD): δ 7.907-7.22 (m, 13H), 6.13-6.00 (m, 1H), 4.68-4.35(m, 2H), 4.46 (S, 2H), 4.10-3.40 (m, 12H).

EXAMPLE 35 (44)4-Diethylcarbamoylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2036]

[2037] TLC: Rf 0.40 (ethyl acetate);

[2038] NMR (CDCl₃): δ 7.83-7.77 (m, 2H), 7.68-7.59 (m, 1H), 7.56-7.45(m, 3H), 7.32 (d, J=7.6 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 5.44 (d,J=8.8Hz, 1H), 4.59 (d, J=14.5 Hz, 1H), 4.51 (d, J=14.5 Hz, 1H), 4.15 (d,J=15.0 Hz, 1H), 3.74 (dd, J=15.0, 8.8 Hz, 1H), 3.39 (q, J=7.0 Hz, 2H),3.30 (q, J=7.0 Hz, 2H), 1.22 (t, J=7.0 Hz, 3H), 1.14 (t, J=7.0 Hz, 3H).

EXAMPLE 35 (45)4-Cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2039]

[2040] TLC: Rf 0.27 (hexane:ethyl acetate=1:2);

[2041] NMR (DMSO-d₆): δ 7.82-7.72 (m, 4H), 7.68-7.60 (m, 2H), 7.50 (d,J=8.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 5.60 (dd, J=9.0, 1.2 Hz, 1H),5.04 (d, J=16.0 Hz, 1H), 4.90 (d, J=16.0 Hz, 1H), 4.20 (dd, J=15.2, 1.2Hz, 1H), 4.00 (dd, J=15.2, 9.0 Hz, 1H).

EXAMPLE 35 (46) 5-(Pyridin-3-yloxy)methyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2042]

[2043] Free Compound:

[2044] TLC: Rf 0.27 (ethyl acetate);

[2045] NMR (CDCl₃): δ 8.37-8.36 (m, 1H), 8.31-8.29 (m, 1H), 7.76-7.71(m, 3H), 7.66-7.61 (m, 1H), 7.49-7.43 (m, 3H), 7.27-7.25 (m, 2H), 5.25(dd, J=9.5,1.0 Hz, 1H), 5.16 (d, J=12.5 Hz, 1H), 5.12 (d, J=12.5 Hz,1H), 4.15 (dd, J=15.0,1.0 Hz, 1H), 3.90 (s, 3H), 3.81 (dd, J=15.0, 9.5Hz, 1H)

[2046] Hydrochloride:

[2047] TLC: Rf 0.27 (ethyl acetate);

[2048] NMR (DMSO-d₆): δ 8.76 (d, J=2.5 Hz, 1H), 8.52 (d, J=5.0 Hz, 1H),8.15 (dd, J=8.5, 2.5 Hz, 1H), 7.93-7.74 (m, 5H), 7.65-7.60 (m, 3H), 5.78(d, J=8.5 Hz, 1H), 5.35 (s, 2H), 4.17 (d, J=15.0 Hz, 1H), 4.06 (dd,J=15.0, 8.5 Hz, 1H), 3.69 (s, 3H).

EXAMPLE 35 (47) 5-(2-(t-Butoxycarbonylamino)ethyl)oxy-4-nitro-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2049]

[2050] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2051] NMR (CDCl₃): δ 7.86-7.70 (m, 4H), 7.63-7.54 (m, 2H), 7.41 (d,J=8.8 Hz, 1H), 5.69 (dd, J=9.0, 1.8 Hz, 1H), 5.07 (br, 1H), 4.38-4.22(m, 2H), 3.90 (dd, J=15.0, 1.8 Hz, 1H), 3.75 (dd, J=15.0, 9.0 Hz, 1H),3.68-3.52 (m, 2H), 1.46 (s, 9H).

EXAMPLE 35 (48)5-((2E)-3-Ethoxycarbonyl-2-propenyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2052]

[2053] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[2054] NMR (CDCl₃): δ 5 7.72-7.65 (m, 3H), 7.62-7.46 (m, 4H), 7.15 (dd,J=8.7,2.1 Hz,1H), 7.08 (dt, J=15.6, 4.2 Hz, 1H), 6.20 (dt, J=15.6, 2.1Hz, 1H), 5.01 (dd, J=8.7, 4.8 Hz, 1H), 4.87-4.81 (m, 2H), 4.24 (q, J=7.2Hz, 2H), 3.77 (dd, J=14.7,4.8 Hz, 1H), 3.70 (dd, J=14.7, 8.7 Hz, 1H),1.31 (t, J=7.2 Hz, 3H).

EXAMPLE 35 (49)4-(2,4-Dimethoxyphenylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2055]

[2056] Free Compound:

[2057] TLC: Rf 0.35 (ethyl acetate);

[2058] NMR (CDCl₃): δ 7.69 (dd, J=6.9, 1.5 Hz, 1H), 7.64-7.50 (m, 5H),7.46-7.41 (m, 2H), 7.01 (d, J=8.0 Hz, 1H), 6.45 (d, J=2.5 Hz,1H), 6.43(dd, J=8.0,2.5 Hz,1H), 6.05 (dd, J=9.3, 1.2 Hz, 1H), 4.51 (d, J=14.1 Hz,1H), 3.91 (d, J=14.1 Hz, 1H), 3.85 (dd, J=15.0, 1.2 Hz, 1H), 3.81 (s,3H), 3.78 (s, 3H), 3.73 (d, J=13.0 Hz, 1H), 3.66 (d, J=13.0 Hz, 1H),3.65 (dd, J=15.0, 9.3 Hz, 1H).

[2059] Hydrochloride:

[2060] TLC: Rf 0.35 (ethyl acetate);

[2061] NMR (DMSO-d₆): δ 9.40 (br, 2H), 8.20-8.11 (m, 1H), 7.86-7.59 (m,7H), 7.42 (d, J 8.4 Hz, 1H), 6.61-6.56 (m, 2H), 6.09 (dd, J=6.8, 3.0 Hz,1H), 4.65 (d, J=13.8 Hz, 1H), 4.38 (d, J=13.8 Hz, 1H), 4.22-4.06 (m,2H), 3.88-3.85 (m, 2H), 3.80 (s, 3H), 3.79 (s, 3H).

EXAMPLE 35 (50)4-(Pyridin-3-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene2hydrochloride

[2062]

[2063] TLC: Rf 0.44 (chloroform:methanol=9:1);

[2064] NMR (CD₃OD): δ 9.21 (s, 1H), 8.95 (d, J=5.6 Hz, 1H), 8.92-8.84(m, 1H), 8.22 (dd, J=6.6, 2.2 Hz, 1H), 8.16 (dd, J=8.0, 5.6 Hz, 1H),7.93-7.74 (m, 5H), 7.68-7.58 (m, 2H), 6.20 (dd, J=8.6, 1.6 Hz, 1H), 4.96(d, J=13.2 Hz, 1H), 4.83-4.70 (m, 3H), 3.92 (dd, J=15.4, 8.6 Hz, 1H),3.77 (dd, J=15.4, 1.6 Hz, 1H).

EXAMPLE 35 (51)4-(2-Dimethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[2065]

[2066] TLC: Rf 0.51 (chloroform:methanol:triethylamine=9:1:1);

[2067] NMR (DMSO-d₆): δ 10.85-10.50 (br, 1H), 10.10-9.75 (br, 1H),9.72-9.40 (br, 1H), 8.22 (dd, J=5.4, 3.0 Hz, 1H), 7.90-7.85 (m, 2H),7.82-7.75 (m, 3H), 7.67-7.59 (m, 2H), 6.47 (t like, J=1.5 Hz, 1H), 4.72(brd, J=12.0 Hz, 1H), 4.51 (brd, J=12.0 Hz, 1H), 3.91-3.84 (m, 2H),3.70-3.30 (m, 4H), 2.85 (s, 6H).

EXAMPLE 35 (52)4-(N,N-Bis(2-hydroxyethyl)amino)methyl-3-phenylsulfonyl-2,3-dlhydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2068]

[2069] TLC: Rf 0.53 (chloroform:methanol=9:1);

[2070] NMR (DMSO-d₆): δ 10.15-9.90 (br, 1H), 8.24 (d, J=6.6 Hz, 1H),7.95-7.72 (m, 5H), 7.69-7.58 (m, 2H), 6.16 (d, J=8.7 Hz, 1H), 5.80-5.10(br, 2H), 5.11 (brd, J=13.8 Hz, 1H), 4.70 (brd, J=13.8 Hz, 1H), 4.02(dd, J=15.0, 8.7 Hz, 1H), 3.94-3.70 (m, 4H), 3.82 (d, J=15.0 Hz, 1H),3.47-3.18 (m, 3H), 3.12-2.92 (m, 1H).

EXAMPLE 35 (53)4-(2-(2-Hydroxyethoxy)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2071]

[2072] TLC: Rf 0.46 (methylene chloride:methanol=9:1);

[2073] NMR (DMSO-d₆): δ 9.40-9.10 (br, 2H), 8.16 (dd, J=6.3, 2.4 Hz,1H), 7.91-7.75 (m, 5H), 7.68-7.59 (m, 2H), 6.29 (dd, J=7.5, 2.4 Hz, 1H),4.90-4.30 (br, 1H), 4.75-4.63 (m, 1H), 4.50-4.35 (m, 1H), 3.90 (dd, J=15.6, 7.5 Hz, 1H), 3.84 (dd, J=15.6, 2.4 Hz, 1H), 3.74 (t, J=5.1 Hz, 2H),3.58-3.47 (m, 4H), 3.28-3 15 (m, 2H).

EXAMPLE 35 (54)4-(4-Benzylpiperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2074]

[2075] Free Compound:

[2076] TLC: Rf 0.29 (chloroform:methanol=19:1);

[2077] NMR (CDCl₃): δ 7.68-7.57 (m, 4H), 7.56-7.50 (m, 2H), 7.50-7.42(m, 2H), 7.36-7.20 (m, 5H), 6.33 (d, J=9.0 Hz, 1H), 4.69 (d, J=14.1 Hz,1H), 3.90 (d, J=15.0 Hz, 1H), 3.72 (dd, J=15.0, 9.0 Hz, 1H), 3.51 (s,2H), 3.41 (d, J=14.1 Hz,1H), 2.70-2.25 (m, 8H).

[2078] 2hydrochloride:

[2079] TLC: Rf 0.29 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ8.30-7.95 (br, 1H), 7.93-7.72 (m, 5H), 7.70-7.55 (m, 4H), 7.50-7.40 (m,3H), 6.65-6.20 (br, 1H), 5.40-4.20 (br, 4H), 4.50-4.10 (br, 2H), 3.98(dd, J=15.6, 9.0 Hz, 1H), 3.84 (d, J=15.6 Hz, 1H), 3.70-2.80 (m, 6H).

EXAMPLE 35 (55) 4-(4-(Pyridin-2-yl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2080]

[2081] Free Compound:

[2082] TLC: Rf 0.43 (chloroform:methanol 19:1);

[2083] NMR (CDCl₃): δ 8.23-8.16 (m, 1H), 7.71-7.52 (m, 6H), 7.52-7.42(m, 3H), 6.68-6.62 (m, 2H), 6.30 (d, J=9.0 Hz, 1H), 4.76 (d, J=14.1 Hz,1H), 3.89 (d, J=15.0 Hz, 1H), 3.73 (dd, J=15.0, 9.0 Hz, 1H), 3.62-3. 45(m, 4H), 3.49 (d, J=14.1 Hz, 1H), 2.73-2.61 (m, 2H), 2.58-2.44 (m, 2H).3hydrochloride:

[2084] TLC: Rf 0.43 (chloroform:methanol=19:1);

[2085] NMR (DMSO-d₆): δ 12.05-11.70 (br, 1H), 8.35 (d, J=6.3 Hz, 1H),8.15-8.09 (m, 1H), 7.96-7.84 (m, 3H), 7.83-7.75 (m, 3H), 7.68-7.58 (m,2H), 7.24 (d, J=8.7 Hz,1H), 6.93 (t, J=6.3 Hz, 1H), 6.46 (d, J=8.7Hz,1H), 4.87 (d, J=13.8 Hz, 1H), 4.62 (d, J=13.8 Hz, 1H), 4.55-4.30 (m,2H), 4.00 (dd, J=15.0, 8.7 Hz, 1H), 3.83 (d, J=15.0 Hz, 1H), 3.72-3.50(m, 2H), 3.50-3.15 (m, 4H).

EXAMPLE 35 (56) 4-(4-Ethoxycarbonylpiperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2086]

[2087] Free Compound:

[2088] TLC: Rf 0.45 (chloroform:methanol 19:1);

[2089] NMR (CDCl₃): δ 7.69-7.52 (m, 6H), 7.51-7.41 (m, 2H), 6.16 (d,J=9.0 Hz, 1H), 4.71 (d, J=14.4 Hz, 1H), 4.15 (q, J=7.2 Hz, 2H), 3.91 (d,J=15.0 Hz, 1H), 3.74 (dd, J=15.0, 9.0 Hz, 1H), 3.54-3.39 (m, 5H),2.55-2.46 (m, 2H), 2.41-2.29 (m, 2H), 1.27 (t, J=7.2 Hz, 3H).

[2090] Hydrochloride:

[2091] TLC: Rf 0.45 (chloroform:methanol=19:1);

[2092] NMR (DMSO-d₆): δ 11.60-11.30 (br, 1H), 8.40-8.20 (br, 1H),8.00-7.74 (m, 5H), 7.68-7.58 (m, 2H), 6.31 (brd, J=8.1 Hz, 1H),4.98-4.70 (m, 1H), 4.70-4.52 (m, 1H), 4.20-3.89 (m, 2H), 4.07 (q, J=7.2Hz, 2H), 3.82 (d, J=15.3 Hz, 1H), 3.77-3.60 (m, 1H), 3.52-2.90 (m, 6H),1.18 (t, J=7.2 Hz, 3H).

EXAMPLE 35 (57)4-(4-(2-Hydroxyethyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2093]

[2094] Free Compound:

[2095] TLC: Rf 0.31 (chloroform:methanol=9:1);

[2096] NMR (CDCl₃): δ 7.70-7.50 (m, 6H), 7.50-7.41 (m, 2H), 6.29 (d,J=9.0 Hz, 1H), 4.72 (d, J=14.1 Hz, 1H), 3.91 (d, J=15.0 Hz, 1H), 3.73(dd, J=15.0, 9.0 Hz, 1H), 3.63 (t, J=5.1 Hz, 2H), 3.43 (d, J=14.1 Hz,1H), 2.80-2.30 (m, 10H).

[2097] 2hydrochloride:

[2098] TLC. Rf 0.31 (chloroform:methanol=9:1);

[2099] NMR (DMSO-d₆): δ 11.50-10.60 (br, 1H), 8.30-8.00 (br, 1H),7.88-7.73 (m, 5H), 7.67-7.58 (m, 2H), 6.60-6.30 (br, 1H), 5.80-4.92 (br,2H), 4.92-4.10 (br, 1H), 3.99 (dd, J=15.0, 8.7 Hz, 1H), 3.86 (d, J=15.0Hz, 1H), 3.81-3.74 (m, 2H), 3.73-2.80 (m, 10H).

EXAMPLE 35 (58)4-(4-(Pyridin-4-yl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2100]

[2101] free compound:

[2102] TLC: Rf 0.36 (chloroform:methanol=9:1);

[2103] NMR (DMSO-d₆): δ 8.14 (d, J=6.6 Hz, 2H), 7.88-7.81 (m, 1H),7.81-7.74 (m, 3H), 7.74-7.68 (m, 2H), 7.67-7.59 (m, 2H), 6.78 (d, J=6.6Hz, 2H), 6.21 (d, J=9.0 Hz, 1H), 4.16 (d, J=14.4 Hz, 1H), 4.05 (dd,J=15.0, 9.0 Hz, 1H), 3.86 (d, J=15.0 Hz, 1H), 3.57 (d, J=14.4 Hz, 1H),3.42-3.18 (m, 4H), 2.43 (t, J=4.8 Hz, 4H). 3hydrochloride:

[2104] TLC: Rf 0.36 (chloroform:methanol=9:1);

[2105] NMR (DMSO-d₆): δ 14.20-13.80 (br, 1H), 12.30-11.90 (br, 1H),8.46-8.20 (br, 1H), 8.35 (d, J=6.9 Hz, 2H), 7.98-7.82 (m, 2H), 7.82-7.74(m, 3H), 7.67-7.57 (m, 2H), 7.25 (d, J=6.9 Hz, 2H), 6.48 (brd, J=8.7Hz,1H), 5.05-4.75 (m, 1H), 4.75-4.52 (m,1H), 4.52-4.15 (m, 2H), 3.98(dd, J=15.3, 8.7 Hz, 1H), 3.95-3.55 (m, 6H), 3.84 (d, J=15.3 Hz, 1H).

EXAMPLE 35 (59)4-Benzylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2106]

[2107] Free Compound:

[2108] TLC: Rf 0.46 (ethyl acetate);

[2109] NMR (CDCl₃): δ 7.74 (dd, J=7.2, 1.5 Hz, 1H), 7.65-7.51 (m, 5H),7.45-7.40 (m, 2H), 7.36-7.25 (m, 5H), 5.84 (dd, J=9.3, 1.0 Hz, 1H), 4.49(d, J=14.1 Hz, 1H), 3.98 (d, J 14.1 Hz, 1H), 3.85 (d, J=12.7 Hz, 1H),3.84 (dd, J=15.0, 1.0 Hz, 1H), 3.77 (d, J=12.7, 1H), 3.65 (dd, J=15.0,9.3 Hz, 1H).

[2110] Hydrochloride:

[2111] TLC: Rf 0.49 (ethyl acetate:triethylamine=6:0.5);

[2112] NMR (DMSO-d₆): δ 9.87 (brs, 1H), 9.57 (brs, 1H), 8.16 (d, J=6.6Hz, 1H), 7.90-7.75 (m, 3H), 7.75-7.57 (m, 6H), 7.50-7.41 (m, 3H),6.33-6.25 (m, 1H), 4.67 (d, J=13.5 Hz, 1H), 4.40 (d, J=13.5 Hz, 1H),4.30 (s, 2H), 3.93-3.80 (m, 2H).

EXAMPLE 35 (60)4-(1-benzylpiperidin-4-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2113]

[2114] Free Compound:

[2115] TLC: Rf 0.30 (ethyl acetate:methanol=2:1);

[2116] NMR (CDCl₃): δ 7.70 (dd, J=7.3, 1.3 Hz, 1H), 7.65-7.41 (m, 7H),7.32-7.24 (m, 5H), 6.09 (dd, J=9.3, 1.0 Hz, 1H), 4.61 (d, J=14.0 Hz,1H), 3.98 (d, J=14.0 Hz, 1H), 3.87 (dd, J=15.0, 1.0 Hz, 1H), 3.72 (dd,J=15.0, 9.3 Hz, 1H), 3.50 (s, 2H), 2.90-2.81 (m, 2H), 2.58-2.51 (m, 1H),2.09-1.96 (m, 3H), 1.83-1.79 (m, 1H), 1.52-1.38 (m, 2H).

[2117] 2hydrochloride:

[2118] TLC: Rf 0.30 (ethyl acetate:methanol=2:1);

[2119] NMR (CD₃OD): δ 8.16-8.12 (m, 1H), 7.91-7.74 (m, 5H), 7.65-7.49(m, 7H), 6.06 (dd, J=8.4, 1.8 Hz, 1H), 4.84-4.68 (m, 2H), 4.36 (br, 2H),3.90 (dd, J=15.4, 8.4 Hz, 1H), 3.77 (dd, J=15.4, 1.8 Hz, 1H), 3.80-3.60(m, 3H), 3.30-3.15 (m, 2H), 2.58-2.43 (m, 2H), 2.35-2.13 (m, 2H).

EXAMPLE 35 (61)4-(Morpholin-4-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2120]

[2121] Free Compound:

[2122] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2123] NMR (CDCl₃): δ 7.68-7.51 (m, 6H), 7.48-7.42 (m, 2H), 6.21 (dd,J=9.3, 0.9 Hz, 1H), 4.68 (d, J=14.3 Hz, 1H), 3.91 (dd, J=15.0, 0.9 Hz,1H), 3.74 (dd, J=15.0, 9.3 Hz, 1H), 3.74-3.64 (m, 4H), 3.45 (d, J=14.3Hz, 1H), 2.58-2.52 (m, 2H), 2.40-2.33 (m, 2H).

[2124] Hydrochloride:

[2125] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2126] NMR (DMSO-d₆): δ 11.48 (br, 1H), 8.31 (d, J=7.2 Hz, 1H),7.94-7.79 (m, 5H), 7.68-7.62 (m, 2H), 6.44 (d, J=8.1 Hz, 1H), 4.85-4.79(m, 1H), 4.62-4.57 (m, 1H), 4.05-3.81 (m, 6H), 3.50-3.13 (m, 4H).

EXAMPLE 35 (62)4-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2127]

[2128] TLC: Rf 0.18 (methylene chloride);

[2129] NMR (CDCl₃): δ 8.24 (dd, J=7.8 Hz, 1.5 Hz, 1H), 7.86 (dd, J=7.8Hz, 1.5 Hz, 1H), 7.75 (t, J=7.8 Hz, 1H), 7.71-7.64 (m, 3H), 7.56-7.47(m, 2H), 6.19 (dd, J=9.3 Hz, 1.5 Hz, 1H), 4.53-4.40 (m, 2H), 3.94 (dd,J=15.0 Hz, 1.5 Hz, 1H), 3.77 (dd, J=15.0 Hz, 9.3 Hz, 1H), 1.47 (t, J=7.2Hz, 3H).

EXAMPLE 35 (63)4-Benzyloxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2130]

[2131] TLC: Rf 0.37 (chloroform:ethyl acetate=19:1);

[2132] NMR (CDCl₃): δ 8.26 (dd, J=7.5, 1.2 Hz, 1H), 7.85 (dd, J=7.8, 1.2Hz, 1H), 7.78-7.70 (m, 1H), 7.69-7.60 (m, 3H), 7.55-7.47 (m, 4H),7.47-7.35 (m, 3H), 6.13 (dd, J=9.3, 1.2 Hz, 1H), 5.45 (d, J=12.3 Hz,1H), 5.40 (d, J=12.3 Hz, 1H), 3.91 (dd, J=15.0, 1.2 Hz, 1H), 3.73 (dd,J=15.0, 9.3 Hz, 1H).

EXAMPLE 35 (64)4-(Pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2133]

[2134] TLC: Rf 0.55 (chloroform:methanol=9:1);

[2135] NMR (DMSO-d₆): δ 9.11 (s, 1H), 8.86 (d, J=5.4 Hz, 1H), 8.57 (d,J=5.4 Hz, 1H), 7.99-7.84 (m, 4H), 7.73-7.64 (m, 1H), 7.53-7.43 (m, 2H),7.42-7.35 (m, 2H), 5.99 (dd, J=7.2, 3.0 Hz, 1H), 4.07 (dd, J=15.3, 7.2Hz, 1H), 4.01 (dd, J=15.3, 3.0 Hz, 1H).

EXAMPLE 35 (65)6-(Pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2136]

[2137] TLC: Rf 0 60 (chloroform:methanol 9:1);

[2138] NMR (DMSO-d₆): δ 9.29 (d, J=2.1 Hz, 1H), 8.85 (d, J=5.1 Hz, 1H),8.76 (d, J=7.8 Hz, 1H), 8.37 (s, 1H), 8.29 (dd, J=8.4, 2.1 Hz, 1H), 7.96(dd, J=8.4, 5.1 Hz, 1H), 7.89-7.75 (m, 4H), 7.71-7.60 (m, 2H), 5.93 (dd,J=9.3, 3.0 Hz, 1H), 4.06 (dd, J=15.0, 9.3 Hz, 1H), 3.85 (dd, J=15.0, 3.0Hz, 1H).

EXAMPLE 35 (66)4-(4,4-Dimethyl-4,5-dihydroxazol-2-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2139]

[2140] TLC: Rf 0.22 (ethyl acetate:hexane=1:1);

[2141] NMR (CDCl₃): δ 8.23 (d, J=6.0 Hz, 1H), 7.73-7.67 (m, 2H),7.67-7.54 (m, 3H), 7.48-7.40 (m, 2H), 6.36 (dd, J=9.0 Hz, 1.8 Hz, 1H),4.26 (d, J=7.5 Hz, 1H), 4.22 (d, J=7.5 Hz, 1H), 3.89 (dd, J=15.0 Hz, 1.8Hz, 1H), 3.78 (dd, J=15.0 Hz, 9.0 Hz, 1H), 1.50 (s, 3H), 1.45 (s, 3H).

EXAMPLE 35 (67)6-Bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2142]

[2143] TLC: Rf 0.24 (methylene chloride);

[2144] NMR (DMSO-d₆): δ 8.13 (d, J=2.0 Hz, 1H), 8.02 (dd, J=8.5, 2.0 Hz,1H), 7.83-7.76 (m, 3H), 7.67-7.60 (m, 3H), 5.79 (dd, J=9.5, 3.0 Hz, 1H),4.05 (dd, J=15.5, 9.5 Hz, 1H), 3.85 (dd, J=15.5, 3.0 Hz, 1H).

EXAMPLE 35 (68)6-Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2145]

[2146] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2147] NMR (DMSO-d₆): δ 7.79-7.71 (m, 3H), 7.64-7.56 (m, 2H), 7.28 (d,J=8.5 Hz, 1H), 6.89 (dd, J=8.5, 2.2 Hz, 1H), 6.68 (d, J=2.2 Hz, ₁H),6.00 (s, 2H), 5.47 (dd, J=9.2,3.0 Hz, 1H), 3.89 (dd, J=15.2, 9.2 Hz,1H), 3.64 (dd, J=15.2, 3.0 Hz, 1H).

EXAMPLES 36˜36 (3)

[2148] By the same procedure as described in Example 28 using carboxylicacid corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and aminecorresponding to (pyridin-3-ylmethyl)amine, the following compounds ofthe present invention were obtained.

EXAMPLE 36 5-Methylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2149]

[2150] TLC: Rf 0.38 (methanol:ethyl acetate=5:95);

[2151] NMR(DMSO-d₆): δ 8.40 (d, J=4.8 Hz, 1H), 7.75 (d, J=7.0 Hz, 1H),7.65 (d, J=7.8 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.44 (d, J=7.0 Hz, 1H),3.89 (s, 3H), 2.78 (d, J=4.8 Hz, 3H).

EXAMPLE 36 (1) 4-Dimethylcarbamoyl-1,1-dioxidebenzo[b]thiophene

[2152]

[2153] TLC: Rf 0.34 (methanol:ethyl acetate=5:95);

[2154] NMR(CDCl₃): δ 7.76 (dd, J=7.0 Hz, 1.4 Hz, 1H), 7.58 (t, J=7.0 Hz,1H), 7.51 (dd, J=7.0 Hz, 1.4 Hz, 1H), 7.33 (d, J=6.8 Hz, 1H), 6.78 (d,J=6.8 Hz, 1H), 3.17 (s, 3H), 3.00 (s, 3H).

EXAMPLE 36 (2) 4-Carbamoyl-1,1-dioxidebenzo[b]thiophene

[2155]

[2156] TLC: Rf 0.50 (methanol:ethyl acetate=5:95);

[2157] NMR(DMSO-d₆): δ 8.22 (brs, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.88 (d,J=8.0 Hz, 1H), 7.78 (brs, 1H), 7.67 (t, J=8.0 Hz, 1H), 7.55 (d, J=8.0Hz, 1H), 7.43 (d, J=7.2 Hz, 1H).

EXAMPLE 36 (3)4-(Furan-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2158]

[2159] TLC: Rf 0.36 (ethyl acetate:hexane 1;1); NMR (CDCl₃+DMSO-d₆): δ7.96 (dd, J=7.2, 0.9 Hz, 1H), 7.81-7.76 (m, 2H), 7.56 (t, J=7.8 Hz, 1H),7.51 (t, J=5.7 Hz, 1H), 7.40-7.38 (m, 1H), 6.78 (d, J=7.2 Hz, 1H),6.37-6.30 (m, 2H), 4.62 (d, J=5.7 Hz, 2H).

EXAMPLES 37˜37 (6)

[2160] By the same procedure as described in Example 18 using an alcoholderivative corresponding to the compound prepared in Example 9 (12) anda halogenated compound corresponding to 4-nitrobenzylbromide, or by thesame procedure as described in Example 29 using an alcohol derivativecorresponding to 4-hydroxy-1,1-dioxidebenzo[b]thiophene and an alcoholderivative corresponding to 1-(3-hydroxypropyl)pyrrole, the followingcompounds of the present invention were obtained.

EXAMPLE 37 4-(2-(Pyridin-4-yl)ethyl) oxy-1,1-dioxidebenzo[b]thiophene

[2161]

[2162] TLC: Rf 0.23 (hexane:ethyl acetate=1:3);

[2163] NMR (CDCl₃): δ 8.56 (d, J=6.0 Hz, 2H), 7.46 (t, J=8.0 Hz, 1H),7.31 (d, J=7.2 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.21 (d, J=6.0 Hz, 2H),7.04 (d, J=8.0 Hz, 1H), 6.60 (d, J=7.2 Hz, 1H), 4.33 (t, J=6.5 Hz, 2H),3.14 (t, J=6.5 Hz, 2H).

EXAMPLE 37 (1) 4-(2-(Pyridin-3-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2164]

[2165] TLC: Rf 0.38 (ethyl acetate);

[2166] NMR(CDCl₃): δ 8.56 (d, J=1.8 Hz, 1H), 8.52 (dd, J=4.8, 1.8 Hz,1H), 7.60 (d, J=8.2 Hz, 1H), 7.45 (t, J=7.6 Hz, 1H), 7.35 (d, J=7.6 Hz,1H), 7.28 (dd, J=7.0 Hz, 1H), 7.26 (d, J=7.6 Hz, 1H), 7.03 (d, J=8.2 Hz,1H), 6.60 (d, J=7.0 Hz, 1H), 4.30 (t, J=6.4 Hz, 2H), 3.15 (t, J=6.4 Hz,2H).

EXAMPLE 37(2) 4-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2167]

[2168] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[2169] NMR (CDCl₃): δ 7.53 (d, J=7.2 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H),7.34 (d, J=8.0 Hz, 1H), 6.94 (d, J=8.0 Hz, 1H), 6.65 (d, J=7.2 Hz, 1H),4.72 (s, 2H), 4.27 (q, J=7.0 Hz, 2H), 1.30 (t, J=7.0 Hz, 3H).

EXAMPLE 37 (3) 6-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2170]

[2171] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[2172] NMR (CDCl₃): “ 7.28 (d, J=8.4 Hz, 1H), 7.24 (d, J=2.6 Hz,1H),7.17 (d, J=7.0 Hz, 1H), 7.05 (dd, J=8.4,2.6 Hz, 1H), 6.63 (d, J=7.0 Hz,1H), 4.68 (s, 2H), 4.29 (q, J=7.0 Hz, 2H), 1.31 (t, J=7.0 Hz, 3H).

EXAMPLE 37 (4) 6-Cyanomethyloxy-1,1-dioxidebenzo[b]thiophene

[2173]

[2174] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[2175] NMR (CDCl₃): δ 7.36 (d, J=8.4Hz,1H), 7.34 (dd, J=2.6,0.8Hz, 1H),7.20 (dd, J=7.0, 0.8 Hz, 1H), 7.14 (dd, J=8.4, 2.6 Hz, 1H), 6.69 (d,J=7.0 Hz,1H), 4.84 (s, 2H).

EXAMPLE 37 (5) 5-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2176]

[2177] TLC: Rf 0.31 (ethyl acetate:hexane=1:1);

[2178] NMR (CDCl₃): δ 7.64 (d, J=8.2 Hz, 1H), 7.15 (d, J=6.8 Hz, 1H),6.98-6.86 (m,2H), 6.74 (d, J=6.8 Hz, 1H), 4.69 (s, 2H), 4.29 (q, J=7.2Hz, 2H), 1.31 (t, J=7.2 Hz, 3H).

EXAMPLE 37 (6) 7-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2179]

[2180] TLC: Rf 0.28 (ethyl acetate:hexane=1:1);

[2181] NMR (CDCl₃): δ 7.46 (dd, J=8.6 Hz, 7.0 Hz, 1H), 7.14 (d, J=7.0Hz, 1H), 6.96 (d, J=7.0 Hz,1H), 6.89 (d, J=8.6 Hz,1H), 6.68 (d, J=7.0Hz,1H), 4.84 (s, 2H), 4.28 (q, J=7.0 Hz, 2H), 1.29 (t, J=7.0 Hz, 3H).

EXAMPLES 38˜38 (3)

[2182] By the same procedure as described in Example 32 using acarboxylic acid derivative corresponding to4-carboxy-1,1-dioxidebenzo[b]thiophene and a halogenated compoundcorresponding to bromoethane, the following compounds of the presentinvention having the following physical data were obtained.

EXAMPLE 38 5-Benzyloxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2183]

[2184] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[2185] NMR (CDCl₃): δ 7.98 (d, J=8.0 Hz, 1H), 7.51-7.36 (m, 7H), 6.73(d, J=7.0 Hz, 1H), 5.38 (s, 2H), 3.87 (s, 3H).

EXAMPLE 38 (1) 5-Ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[2186]

[2187] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2188] NMR (CDCl₃): δ 8.22 (dd, J=8.0, 1.0 Hz, 1H), 8.03 (d, J=1.0 Hz,1H),7.79 (d, J=8.0 Hz, 1H), 7.15 (d, J=7.0 Hz, 1H), 6.80 (d, J=7.0 Hz,1H), 4.43 (q , J=7.0 Hz,1H), 1.42 (t, J=7.0 Hz,, 3H).

EXAMPLE 38 (2) 7-Methoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[2189]

[2190] TLC: Rf 0.15 (hexane:ethyl acetate=2:1);

[2191] NMR (CDCl₃): δ 8.11 (d, J=8 Hz, 1H), 7.66 (t, J=8 Hz, 1H), 7.55(d, J=8 Hz, 1H), 7.20 (d, J=7 Hz, 1H), 6.77 (d, J=7 Hz, 1H), 4.05 (s,3H).

EXAMPLE 38 (3) 7-Ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[2192]

[2193] TLC: Rf 0.39 (ethyl acetate:hexane=1:1);

[2194] NMR (CDCl₃): δ 8.13 (dd, J=7.6 Hz, 1.2 Hz, 1H), 7.65 (t, J=7.6Hz, 1H), 7.52 (dd, J=7.6 Hz, 1.2 Hz, 1H), 7.18 (d, J=6.8 Hz, 1H), 6.76(d, J=6.8 Hz, 1H), 4.53 (q, J=7.2 Hz, 2H), 1.48 (t, J=7.2 Hz, 1H).

EXAMPLE 39 5-t-Butoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2195]

[2196] A suspension of 5-carboxy-4-methoxy-1,1-dioxidebenzo[b]thiophene(934 mg) in benzene (15 ml) was refluxed. Thereto was addeddimethylformamidedi-t-butylacetal (4.02 g) dropwise. The mixture wasrefluxed for 1 hour. To the reaction mixture water was added. Themixture was extracted by benzene. The extract was washed by a saturatedaqueous solution of sodium bicarbonate and a saturated aqueous solutionof sodium chloride sucessively, dried over anhydrous sodium sulfate andconcentrated. The residue was purified with column chromatography onsilica gel (ethyl acetate:hexane=1:0) to give the compound of thepresent invention (942 mg) having the following physical data.

[2197] TLC: Rf 0.25 (ethyl acetate:hexane=1:4);

[2198] NMR (CDCl₃): δ 7.87 (d, J=7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H),7.45 (d, J=7.0 Hz, 1H), 6.73 (d, J=7.0 Hz, 1H), 3.95 (s, 3H), 1.62 (s,9H).

EXAMPLE 40 5-((E)-2-(Ethoxycarbonyl)ethenyl)-4-methoxybenzo[b]thiophene

[2199]

[2200] To a suspension of 62.5% sodium hydride (920 mg) in anhydroustetrahydrofuran (40 ml), was added a solution oftriethylphosphonoacetate (5.83 g) in anhydrous tetrahydrofuran (20 ml)dropwise. The mixture was stirred for 15 minutes. To the reactionmixture, was added a solution of 5-formyl-4-methoxybenzo[b]thiophene(3.84 g) in anhydrous tetrahydrofuran (20 ml) dropwise. The mixture wasstirred at room temperature for 1 hour. To the reaction mixture, wasadded acetic acid (1.5 ml). The mixture was concentrated. The residuewas purified with column chromatography on silica gel (hexane:ethylacetate=9:1) to give the compound of the present invention (5.17 g)having the following physical data.

[2201] TLC: Rf 0.37 (hexane:ethyl acetate=5:1);

[2202] NMR (CDCl₃): δ 8.13 (d, J=16.2 Hz, 1H), 7.62-7.41 (m, 4H), 6.53(d, J=16.2 Hz, 1H), 4.29 (q, J=7.2 Hz, 2H), 4.00 (s, 3H), 1.36 (t, J=7.2Hz, 3H).

EXAMPLE 41 5-(2-(Ethoxycarbonyl)ethyl)-4-methoxybenzo[b]thiophene

[2203]

[2204] To a solution of the compound prepared in Example 40 (5.16 g) inethanol (100 ml), 10% palladium carbon (200 mg) was added. Under anatmosphere of hydrogen the mixture was stirred at room temperature. Thereaction mixture was filtrated through celite, and the filtrate wasconcentrated. The residue was purified with column chromatography onsilica gel (hexane:ethyl acetate=9:1) to give the compound of thepresent invention (3.23 g) having the following physical data.

[2205] TLC: Rf 0.40 (hexane:ethyl acetate=5:1);

[2206] NMR (CDCl₃): δ 6 7.56 (d, J=8.1 Hz, 1H), 7.41 (q, J=5.4 Hz, 2H),7.20 (d, J=8.1 Hz, 1H), 4.14 (q, J=7.2 Hz, 2H), 3.97 (s, 3H), 3.07 (t,J=8.0 Hz, 2H), 2.66 (t, J=8.0 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H).

EXAMPLE 425-(2-(Ethoxycarbonyl)ethyl)-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2207]

[2208] By the same procedure as described in 3 using the compoundprepared in Example 41 instead of the compound prepared in Example 1,the compound of the present invention having the following physical datawas obtained (with the proviso that 3-chloroperbenzoic acid was usedinstead of OXONE® as an oxidizer).

[2209] TLC: Rf 0.25 (hexane:ethyl acetate=2:1);

[2210] NMR (CDCl₃): δ 7.45-7.36 (m, 3H), 6.70 (d, J=6.8 Hz, 1H), 4.15(q, J=7.4 Hz, 2H), 3.92 (s, 3H), 3.01 (t, J=7.6 Hz, 2H), 2.62 (t, J=7.6Hz, 2H), 1.24 (t, J=7.4 Hz, 3H).

EXAMPLE 435-(4.4-Dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[2211]

[2212] Using the compound which was obtained with using5-carboxy-1,1-dioxidebenzo[b]thiophene and(2-hydroxy-1,1-dimethylethyl)amine instead of4-carboxy-1,1-dioxidebenzo[b]thiophene and (pyridin-3-ylmethyl)aminerespectively, by the same procedure as described in Example 28, by thesame procedure as described in Example 34, the compound of the presentinvention having the following physical data was obtained.

[2213] TLC: Rf 0.39 (ethyl acetate:hexane=1:1);

[2214] NMR (CDCl₃): δ 8.08 (dd, J=8.0 Hz, 1.2 Hz, 1H), 7.98 (d, J=1.2Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.23 (d, J=7.0 Hz, 1H), 6.77 (d, J=7.0Hz, 1H), 4.16 (s, 2H), 1.40 (s, 6H).

EXAMPLES 44˜44 (24)

[2215] By the same procedure as described in Example 1 using thecompounds prepared in Examples 36˜36 (2), Examples 37˜37 (6), Examples38˜38 (3), Example 39, Example 42, Example 36 (3), Example 43 instead of1,1-dioxidebenzo[b]thiophene or a corresponding derivative and thiolderivatives corresponding to thiophenol, the following compounds of thepresent invention were obtained.

EXAMPLE 445-Methylcarbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2216]

[2217] TLC: Rf 0.58 (methanol:ethyl acetate 5:95);

[2218] NMR (CDCl₃): δ 8.10 (d, J=5.6 Hz, 1H), 7.56 (d, J=5.6 Hz, 1H),7.54-7.48 (m, 2H), 7.43-7.35 (m, 3H), 7.17 (brs, 1H), 5.07 (dd, J=4.6Hz, 1.4 Hz, 1H), 4.04 (s, 3H), 3.72 (dd, J=9.4 Hz, 4.6 Hz, 1H), 3.63(dd, J=9.4 Hz, 1.4 Hz, 1H), 3.07 (d, J=4.8 Hz, 3H).

EXAMPLE 44 (1) 4-Dimethylcarbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2219]

[2220] TLC: Rf 0.52 (methanol:ethyl acetate=5:95);

[2221] NMR (CDCl₃): δ 7.78 (dd, J=7.5 Hz, 1.8 Hz, 1H), 7.63-7.51 (m,4H), 7.43-7.34 (m, 3H), 5.41 (dd, J=7.8 Hz, 1.8 Hz, 1H), 3.74 (dd,J=14.1 Hz, 7.8 Hz, 1H), 3.61 (dd, J=14.1 Hz, 1.8 Hz, 1H), 3.17 (s, 3H),3.00 (s, 3H).

EXAMPLE 44 (2)4-Carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2222]

[2223] TLC: Rf 0.49 (methanol:ethyl acetate=5:95);

[2224] NMR (DMSO-d₆): δ 8.19 (brs, 1H), 7.96-7.64 (m, 4H), 7.52-7.30 (m,5H), 5.87 (d, J=7.4 Hz, 1H), 4.10 (dd, J=14.6 Hz, 7.4 Hz, 1H), 3.61 (d,J=14.6 Hz, 1H).

EXAMPLE 44 (3)4-(2-(Pyridin-4-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-11-dioxidebenzo[b]thiophene

[2225]

[2226] TLC: Rf 0.44 (ethyl acetate:methanol=10:1);

[2227] NMR (CDCl₃): δ 8.50 (d, J=6 Hz, 2H), 7.60-7.13 (m, 9H), 7.07 (d,J=8 Hz, 1H), 4.93 (dd, J=2, 7 Hz, 1H), 4.50-4.15 (m, 2H), 3.80-3.50 (m,2H), 3.15 (t, J=7 Hz, 2H).

EXAMPLE 44 (4)4-(2-(Pyridin-3-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2228]

[2229] TLC: Rf 0.38 (ethyl acetate);

[2230] NMR (CDCl₃): δ 8.57 (d, J=1.8 Hz, 1H), 8.48 (dd, J=5.0 Hz, 1.8Hz, 1H), 7.63 (m, 1H), 7.54-7.32 (m, 7H), 7.19 (dd, J=7.8 Hz, 4.0 Hz,1H), 7.05 (d, J=8.0 Hz, 1H), 4.97 (dd, J=6.2 Hz, 1.8 Hz, 1H), 4.32 (m,2H), 3.67 (dd, J=14.2 Hz, 6.2 Hz, 1H), 3.58 (dd, J=14.2 Hz, 1.8 Hz, 1H),3.16 (t, J=7.2 Hz, 2H).

EXAMPLE 44 (5)4-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2231]

[2232] TLC: Rf 0.45 (hexane:ethyl acetate=1:1);

[2233] NMR (CDCl₃): δ 7.57-7.53 (m, 2H), 7.49 (d, J=8.1 Hz, 1H),7.38-7.33 (m, 4H), 6.96 (d, J=8.1 Hz, 1H), 5.16 (dd, J=7.0, 1.8 Hz, 1H),4.71 (s, 2H), 4.28 (q, J=7.2 Hz, 2H), 3.72 (dd, J=14.0, 7.0 Hz, 1H),3.62 (dd, J=14.0, 1.8 Hz, 1H), 1.30 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (6)6-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2234]

[2235] TLC: Rf 0.54 (hexane:ethyl acetate=1:1);

[2236] NMR (CDCl₃): δ 7.62 (d, J=8.7 Hz, 1H), 7.43-7.40 (m, 2H),7.35-7.33 (m, 3H), 7.25 (dd, J=8.7, 2.4 Hz, 1H), 7.10 (d, J=2.4 Hz, 1H),4.91 (t, J=6.8 Hz, 1H), 4.66 (s, 2K), 4.28 (q, J=7.2 Hz, 2H), 3.81 (dd,J=13.7, 6.8 Hz, 1H), 3.52 (dd, J=13.7, 6.8 Hz, 1H), 1.31 (t, J=7.2 Hz,3H).

EXAMPLE 44 (7)6-Cyanomethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2237]

[2238] TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

[2239] NMR (CDCl₃): δ 7.69 (d, J=8.4 Hz, 1H), 7.44-7.41 (m, 2H),7.38-7.34 (m, 3H), 7.28 (dd, J=8.4, 2.4 Hz, 1H), 7.24 (d, J=2.4 Hz, 1H),4.93 (t, J=6.9 Hz, 1H), 4.83 (s, 2H), 3.83 (dd, J=13.7, 6.9 Hz 1H) 3.54(dd, J=13.7, 6.9 Hz, 1H).

EXAMPLE 44 (8)5-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2240]

[2241] TLC: Rf 0.45 (ethyl acetate:hexane=1:1);

[2242] NMR (CDCl₃): δ 7.64 (d, J=8.6 Hz, 1H), 7.48-7.30 (m, 5H), 7.15(d, J=2.2 Hz, 1H), 7.06 (dd, J=8.6 Hz, 2.2 Hz, 1H), 4.90 (t, J=7.0Hz,1H), 4.69 (s, 2H), 4.29 (q, J=7.4Hz, 2H), 3.79 (dd, J=13.6 Hz, 7.0 Hz,1H), 3.50 (dd, J=13.6 Hz, 7.0 Hz, 1H), 1.32 (t, J=7.4 Hz, 3H).

EXAMPLE 44 (9)7-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2243]

[2244] TLC: Rf 0.43 (ethyl acetate:hexane=1:1);

[2245] NMR (CDCl₃): δ 7.55 (t, J=8.4 Hz, 1H), 7.46-7.27 (m, 6H), 6.82(d, J=8.4 Hz, 1H), 4.91 (dd, J=7.6 Hz, 6.6 Hz, 1H), 4.80 (s, 2H), 4.26(q, J=7.2 Hz, 2H), 3.80 (dd, J=13.6 Hz, 7.6 Hz, 1H) 3.54 (dd, J=13.6 Hz,6.6 Hz, 1H), 1.28 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (10)5-Benzyloxycarbonyl-4-methoxy-3-phenylethio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2246]

[2247] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[2248] NMR (CDCl₃): δ 7.99 (d, J=8.0 Hz, 1H), 7.54-7.34 (m, 1H), 5.40(s, 2H), 5.08 (dd, J=6.0, 2.5 Hz, 1H), 3.97 (s, 3H), 3.69 (dd, J=14.0,6.0 Hz, 1H), 3.60 (dd, J=14.0, 2.5 Hz, 1H).

EXAMPLE 44 (1 1)5-Ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2249]

[2250] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[2251] NMR (CDCl₃): δ 8.36 (s, 1H), 8.20 (d, J=8.2 Hz, 1H), 7.78 (d,J=8.2 Hz, 1H), 7.47-7.33 (m, 5H), 4.97 (t, J=7.0 Hz, 1H), 4.44 (q, J=7.0Hz, 2H), 3.84 (dd, J=13.7, 7.0 Hz, 1H), 3.54 (dd, J=13.7, 7.0 Hz, 1H),1.43 (t, J=7.0 Hz, 3H).

EXAMPLE 44 (12)7-Methoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2252]

[2253] TLC: Rf 0.39 (ethyl acetate:hexane=1:1);

[2254] NMR (CDCl₃): δ 8.12 (d, J=7.8 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H),7.72 (t, J=7.8 Hz, 1H), 7.48-7.33 (m, 5H), 4.92 (dd, J=7.6 Hz, 6.8 Hz,1H), 4.01 (s, 3H), 3.86 (dd, J=13.6 Hz, 7.6 Hz, 1H), 3.56 (dd, J=1 3.6Hz, 6.8 Hz, 1H).

EXAMPLE 44 (13)7-Ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2255]

[2256] TLC: Rf 0.60 (ethyl acetate:hexane=1:1);

[2257] NMR (CDCl₃): δ 8.13 (d, J=7.8 Hz, 1H), 7.91 (d, J=7.8 Hz, 1H),7.72 (t, J=7.8 Hz, 1H), 7.46-7.38 (m, 2H), 7.38-7.30 (m, 3H), 4.92 (dd,J=7.8 Hz, 6.9 Hz, 1H), 4.48 (q, J=7.2 Hz, 2H), 3.84 (dd, J=13.5 Hz, 7.8Hz, 1H), 3.55 (dd, J=13.5 Hz, 6.9 Hz, 1H), 1.44 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (14)5-t-Butoxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2258]

[2259] TLC: Rf 0.22 (ethyl acetate:hexane 1:4);

[2260] NMR (CDCl₃): δ 7.88 (d, J=8.0 Hz,1H), 7.58-7.49 (m, 2H), 7.46 (d,J=8.0 Hz,1H), 7.43-7.34 (m, 3H), 5.10 (dd, J=6.0 Hz, 2.8 Hz, 1H), 4.08(s, 3H), 3.70 (dd, J=13.8 Hz, 6.0 Hz, 1H), 3.61 (dd, J=13.8 Hz, 2.8 Hz,1H), 1.63 (s, 9H).

EXAMPLE 44 (15)5-(2-(Ethoxycarbonyl)ethyl)4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2261]

[2262] TLC: Rf 0.25 (hexane:ethyl acetate=2:1);

[2263] NMR (CDCl₃): δ 7.55-7.50 (m, 2H), 7.44 (s, 2H), 7.43-7.30 (m,3H), 5.08 (dd, J=6.9, 2.1 Hz, 1H), 4.15 (q, J=7.2 Hz, 2H), 4.05 (s, 3H),3.68 (dd, J=15.2, 7.2 Hz, 1H), 3.60 (dd, J=15.2, 2.1 Hz, 1H), 3.18-3.00(m, 2H), 2.66 (t, J=7.8 Hz, 2H), 1.25 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (16)4-(Furan-2-ylmethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2264]

[2265] TLC: Rf 0.37 (ethyl acetate:benzene=1:2);

[2266] NMR (DMSO-d₆): δ 9.24 (t, J=5.6 Hz, 1H), 7.93-7.82 (m, 2H),7.77-7.66 (m, 1H), 7.55-7.51 (m, 1H), 7.47-7.31 (m, 5H), 6.37-6.29 (m,2H), 5.75 (d, J=7.6 Hz, 1H), 4.46 (d, J=5.6 Hz, 2H), 4.12 (dd, J=14.2Hz, 7.6 Hz, 1H), 3.62 (d, J=14.2 Hz, 1H).

EXAMPLE 44 (17)5-(4,4-Dimethyl-4,5-dihydroxazol-2-yl)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2267]

[2268] TLC: Rf 0.50 (ethyl acetate:hexane=1:1);

[2269] NMR (CDCl₃): δ 8.32 (brs, 1H), 8.12 (d, J=8.2 Hz, 1H), 7.75 (d,J=8.2 Hz, 1H), 7.50-7.30 (m, 5H), 4.96 (dd, J=7.2 Hz, 6.6 Hz, 1H), 4.18(s, 2H), 3.82 (dd, J=13.8 Hz, 7.2 Hz, 1H), 3.54 (dd, J=13.8 Hz, 6.6 Hz,1H), 1.42 (s, 6H).

EXAMPLE 44 (18) 3-Benzylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2270]

[2271] TLC: Rf 0.52 (hexane:ethyl acetate 1:1);

[2272] NMR (CDCl₃): δ 3.42 (dd, J=13.8Hz, 6.3Hz, 1H), 3.69 (dd,J=13.8Hz, 7.8Hz, 1H), 3.78 (d, J=13.7Hz, 1H), 3.86 (d, J=13.7Hz, 1H),4.53 (t-like, J=7.1Hz, 1H), 7.27-7.33 (m, 5H), 7.46-7.56 (m,1H),7.59-7.62 (m, 2H), 7.71 (d, J=7.6Hz, 1H).

EXAMPLE 44 (19)3-(3,4-Dichlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2273]

[2274] TLC: Rf 0.57 (hexane:ethyl acetate=1:1);

[2275] NMR (CDCl₃): δ 3.48 (dd, J=13.6Hz, 5.8Hz, 1H), 3.83 (dd,J=13.6Hz, 7.6Hz, 1H), 4.97 (t-like, J=6.8Hz, 1H), 7.23 (dd, J=8.3Hz,2.2Hz, 1H), 7.41 (d, J=8.3Hz, 1H), 7.51 (d, J=2.2Hz, 1H), 7.54-7.62 (m,1H), 7.66-7.69 (m, 2H), 7.74 (d, J=76Hz, 1H).

EXAMPLE 44 (20)3-(4-Nitrophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2276]

[2277] TLC: Rf 0.15 (methylene chloride); NMR (CDCl₃): δ 3.55 (dd,J=13.8Hz, 6.0Hz, 1H), 3.97 (dd, J=13.8Hz, 7.5Hz, 1H), 5.20 (t-like,J=6.8Hz, 1H), 7.47 (d, J=8.7Hz, 2H), 7.55-7.64 (m, 1H), 7.68-7.70 (m,2H), 7.79 (d, J=7.6Hz,1H), 8.19 (d, J=8.7Hz, 2H).

EXAMPLE 44 (21)5-Hydroxymethyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2278]

[2279] TLC: Rf 0.64 (ethyl acetate);

[2280] NMR (CDCl₃): δ 7.68 (d, J=7.8 Hz, 1H), 7.55-7.47 (m, 3H),7.39-7.35 (m, 3H), 5.08 (dd, J=6.6, 2.5 Hz, 1H), 4.84 (d, J=6.0 Hz, 2H),4.06 (s, 3H), 3.69 (dd, J=13.9, 6.6 Hz, 1H), 3.58 (dd, J=13.9, 2.5 Hz,1H), 2.15 (t, J=6.0 Hz, 1H).

EXAMPLE 44 (22)4-Hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2281]

[2282] TLC: Rf 0.22 (chloroform:ethyl acetate=4:1);

[2283] NMR (CDCl₃): δ 7.77-7.66 (m, 2H), 7.61 (d, J=7.4 Hz, 1H),7.57-7.44 (m, 2H), 7.43-7.32 (m, 3H), 5.20 (dd, J=6.8, 2.0 Hz, 1H), 5.03(s, 2H), 3.72 (dd, J=14.0, 6.8 Hz, 1H), 3.62 (dd, J=14.0, 2.0 Hz, 1H),2.45-2.15 (br,1H).

EXAMPLE 44 (23)6-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2284]

[2285] TLC: Rf 0.62 (ethyl acetate:hexane=1:4);

[2286] NMR (CDCl₃): δ 7.70 (ddd, J=7.6Hz, 4.4Hz, 0.4Hz,1H), 7.47-7.29(m, 7H),4.93 (t, J=7.0 Hz, 1H), 3.84 (dd, J=13.8 Hz, 7.0 Hz, 1H), 3.55(dd, J=13.8 Hz, 7.0 Hz, 1H).

EXAMPLE 44 (24)4-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2287]

[2288] TLC: Rf 0.55 (ethyl acetate:hexane=1:4);

[2289] NMR (CDCl₃): δ 7.64-7.45 (m, 4H), 7.42-7.27 (m, 4H), 5.06 (dd,J=7.4 Hz, 2.8 Hz, 1H), 3.77 (dd, J=14.2 Hz, 7.4 Hz, 1H), 3.63 (dd,J=14.2 Hz, 2.8 Hz, 1H).

EXAMPLES 45˜45 (22)

[2290] Using the compounds prepared in Examples 44˜44 (15) and Examples44 (18)˜44 (24) instead of the compound prepared in Example 1 by thesame procedure as described in Example 3, or by the same reaction using3-chloroperbenzoic acid instead of OXONE@ as an oxidizer, and ifnecessary, by converting into a corresponding salt by known methods, thefollowing compounds of the present invention were obtained.

EXAMPLE 455-Methylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2291]

[2292] TLC: Rf 0.33 (methanol:ethyl acetate=5:95); NMR (DMSO-d₆): δ 8.47(q-like, J=3.4 Hz, 1H), 7.87-7.73 (m, 3H), 7.69-7.60 (m, 3H), 7.50 (d,J=5.4 Hz, 1H), 5.65 (d, J=6.0 Hz, 1H), 4.13 (d, J=10.2 Hz, 1H), 3.98(dd, J=10.2 Hz, 6.0 Hz, 1H), 3.59 (s, 3H), 2.77 (d, J=3.4 Hz, 3H).

EXAMPLE 45 (1)4-Dimethylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2293]

[2294] TLC: Rf 0.55 (methanol:ethyl acetate=5:95);

[2295] NMR (DMSO-d₆): δ 7.93-7.73 (m, 6H), 7.70-7.62 (m, 2H), 5.86 (d,J=9.3 Hz, 1H), 4.12 (dd, J=15.3 Hz, 9.3 Hz, 1H), 3.91 (d, J=15.3 Hz,1H), 3.07 (s, 3H), 3.03 (s, 3H).

EXAMPLE 45 (2)4-Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2296]

[2297] TLC: Rf 0.43 (methanol:ethyl acetate=5:95);

[2298] NMR (DMSO-d₆): δ 8.30 (brs, 1H), 8.03 (d, J=7.8 Hz, 1H), 7.91 (d,J=7.8 Hz, 1H), 7.86-7.72 (m, 5H), 7.68 (brs, 1H), 7.63 (t, J=7.8 Hz,1H), 6.37 (d, J=9.3 Hz, 1H), 4.08 (dd, J=15.3 Hz, 9.3 Hz, 1H), 3.95 (d,J=15.3 Hz, 1H).

EXAMPLE 45 (3)4-(2-Pyridin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2299]

[2300] Free Compound:

[2301] TLC: Rf 0.25 (ethyl acetate:methanol=10:1);

[2302] NMR (CDCl₃): δ 8.58 (d, J=6 Hz, 2H), 7.80-7.35 (m, 6H), 7.35-7.14(m, 3H), 6.98 (d, J=8 Hz, 1H), 5.12 (d, J=9 Hz, 1H), 4.30-4.05 (m, 3H),3.70 (dd, J=9, 15 Hz, 1H), 3.25-2.90 (m, 2H).

[2303] Hydrochloride:

[2304] TLC: Rf 0.25 (ethyl acetate:methanol=10:1);

[2305] NMR (DMSO-d₆): δ 8.83 (d, J=6.6 Hz, 2H), 7.96 (d, J=6.6 Hz, 2H),7.78-7.58 (m, 6H), 7.35-7.30 (m, 2H), 5.40 (d, J=8.5 Hz, 1H), 4.36-4.28(m, 1H), 4.19-4.12 (m, 1H), 4.11 (d, J=15.0 Hz, 1H),3.98 (dd, J=15.0,8.5 Hz, 1H), 3.24-3.15 (m, 1H), 3.11-3.01 (m, 1H).

[2306] Methanesulfonic Acid Salt:

[2307] TLC: Rf 0.25 (ethyl acetate:methanol=10:1);

[2308] NMR (DMSO-d₆): δ 8.85 (d, J=6.6 Hz, 2H), 7.98 (d, J=6.6 Hz, 2H),7.78-7.58 (m, 6H), 7.35-7.30 (m, 2H), 5.39 (d, J=8.5 Hz, 1H), 4.36-4.29(m, 1H), 4.19-4.13 (m, 1H), 4.11 (d, J=15.0 Hz, 1H), 3.97 (dd, J=15.0,8.5 Hz,1H), 3.25-3.17 (m, 1H), 3.11-3.02 (m, 1H).

EXAMPLE 45 (4)4-(2-(Pyridin-3-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1,-dioxidebenzo[b]thiophene.

[2309]

[2310] Free Compound:

[2311] TLC: Rf 013 (ethyl acetate);

[2312] NMR (DMSO-d₆): δ 8.46 (d, J=1.8 Hz, 1H), 8.43 (dd, J=4.8 Hz, 1.8Hz, 1H), 7.86-7.54 (m, 6H), 7.42-7.30 (m, 4H), 5.43 (d, J=7.4Hz, 1H),4.26-3.82, (m, 4H), 2.75 (t, J=6.6 Hz, 2H).

[2313] Hydrochloride:

[2314] TLC: Rf 0.13 (ethyl acetate);

[2315] NMR (DMSO-d₆): δ 8.88 (s, 1H), 8.80 (d, J=5.7 Hz, 1H), 8.49 (d,J=7.8 Hz, 1H), 8.04-7.92 (m, 1H), 7.78-7.54 (m, 6H), 7.30 (d, J=7.8 Hz,1H), 7.29 (d, J=8.4 Hz, 1H), 5.47 (d, J=7.8 Hz, 1H), 4.34-4.20 (m, 1H),4.16-3.91 (m, 3H), 3.19-2.94 (m, 2H).

EXAMPLE 45 (5)4-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2316]

[2317] TLC: Rf 0.17 (hexane:ethyl acetate=1:1);

[2318] NMR (CDCl₃): δ 7.82-7.78 (m, 2H), 7.68-7.60 (m, 1H), 7.58-7.44(m, 3H), 7.36 (d, J=8.0 Hz, 1H), 6.86 (d, J=8.0 Hz, 1H), 5.38 (d, J=8.5Hz, 1H), 4.45 (d, J=16.2 Hz, 1H), 4.30 (d, J=16.2 Hz, 1H), 4.25 (q,J=7.0 Hz, 2H), 4.24 (d, J=15.0 Hz, 1H), 3.76 (dd, J=15.0, 8.5 Hz, 1H),1.30 (t, J=7.0 Hz, 3H).

EXAMPLE 45 (6)6-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2319]

[2320] TLC: Rf 0.31 (hexane:ethyl acetate=1:1);

[2321] NMR (CDCl₃): δ 7.90 (d, J=8.8 Hz, 1H), 7.71-7.62 (m, 3H),7.55-7.46 (m, 2H), 7.30 (dd, J=8.8, 2.4 Hz, 1H), 7.02 (d, J=2.4 Hz, 1H),5.00 (dd, J=7.8, 5.4 Hz, 1H), 4.67 (s, 2H), 4.28 (q, J=7.2 Hz, 2H), 3.80(dd, J=15.0, 5.4 Hz, 1H), 3.72 (dd, J=15.0, 7.8 Hz, 1H), 1.30 (t, J=7.2Hz, 3H).

EXAMPLE 45 (7)6-Cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2322]

[2323] TLC: Rf 0.32 (hexane:ethyl acetate=2:1);

[2324] NMR (DMSO-d₆): δ 7.81-7.75 (m, 3H), 7.68-7.60 (m, 3H), 7.53 (d,J=2.5 Hz, 1H), 7.48 (dd, J=8.5, 2.5 Hz, 1H), 5.73 (dd, J=9.5, 3.0 Hz,1H), 5.33 (s, 2H), 4.03 (dd, J=15.0, 9.5 Hz, 1H), 3.81 (dd, J=15.0, 3.0Hz, 1H).

EXAMPLE 45 (8)5-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2325]

[2326] TLC: Rf 0.35 (ethyl acetate:hexane=1:1);

[2327] NMR (CDCl₃): δ 7.73-7.61 (m, 3H), 7.58-7.45 (m,3H), 7.44 (d,J=2.2 Hz, 1H), 7.18 (dd, J=8.8 Hz, 2.2 Hz, 1H), 5.00 (t, J=7.0 Hz, 1H),4.78 (s, 2H), 4.33 (q, J=7.2 Hz, 2H), 3.81-3.65 (m, 2H), 1.35 (t, J=7.2Hz, 3H).

EXAMPLE 45 (9)7-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2328]

[2329] TLC: Rf 0.17 (ethyl acetate:hexane=1:1);

[2330] NMR (CDCl₃): δ 7.72-7.47 (m, 7H), 6.91 (d, J=6.9 Hz, 1H), 5.03(dd, J=8.7 Hz, 5.4 Hz, 1H), 4.76 (s, 2H), 4.24 (q, J=7.2 Hz, 2H), 3.79(dd, J=14.7 Hz, 5.4 Hz, 1H), 3.73 (dd, J=14.7 Hz, 8 .7 Hz, 1H), 1.27 (t,J=7.2 Hz, 3H).

EXAMPLE 45 (10)5-Benzyloxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2331]

[2332] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[2333] NMR (CDCl₃): δ 7.90 (d, J=8.0 Hz, 1H), 7.76-7.71 (m, 2H),7.63-7.55 (m, 1H), 7.47-7.36 (m, 8H), 5.37 (s, 2H), 5.24 (dd, J=9.0,1.0Hz, 1H), 4.16 (dd, J=15.0, 1.0 Hz, 1H), 3.74 (s, 3H), 3.73 (dd,J=15.0, 9.0 Hz, 1H).

EXAMPLE 45 (11)5-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2334]

[2335] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[2336] NMR (DMSO-d₆): δ 8.23 (d-like, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.97(d, J=8.0 Hz, 1H), 7.85-7.78 (m, 3H), 7.69-7.61 (m, 2H), 5.91 (dd,J=9.3, 3.2 Hz, 1H), 4.38 (q, J=7.0 Hz, 2H), 4.10 (dd, J=15.3, 9.3 Hz,1H), 3.91 (dd, J=15.3, 3.2 Hz; 1H); 1.35 (t, J=7.0 Hz, 3H).

EXAMPLE 45 (12)7-Methoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2337]

[2338] TLC: Rf 0.16 (ethyl acetate:hexane=1:1);

[2339] NMR (CDCl₃): δ 8.23 (d, J=8.1 Hz, 2H), 7.81 (t, J=8.1 Hz, 1H),7.72-7.64 (m, 3H), 7.55-7.47 (m, 2H), 5.07 (dd, J=9.3 Hz, 4.8 Hz, 1H),3.97 (s, 3H), 3.84 (dd, J=14.7 (t, 4.8 Hz, 1H), 3.75 (dd, J=14.7 Hz, 9.3Hz, 1H).

EXAMPLE 45 (13)7-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2340]

[2341] TLC: Rf 0.22 (ethyl acetate:hexane=1:1);

[2342] NMR (CDCl₃): δ 8.25 (d, J=7.8 Hz, 1H), 8.23 (d, J=7.8 Hz, 1H),7.80 (t, J=7.8 Hz, 1H), 7.73-7.65 (m, 3H), 7.56-7.48 (m, 2H), 5.06 (dd,J=9.3 Hz, 4.8 Hz, 1H), 4.44 (q, J=7.2 Hz, 2H), 3.83 (dd, J=14.7 Hz, 4.8Hz, 1H), 3.73 (dd, J=14.7 Hz, 9.3 Hz, 1H), 1.40 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (14)5-t-Butoxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2343]

[2344] TLC: Rf 0.37 (ethyl acetate:hexane 1:1);

[2345] NMR (CDCl₃): δ 7.80 (d, J=8.1 Hz, 1H), 7.78 (d, J=7.8 Hz, 2H),7.66 (t, J=7.8 Hz, 1H), 7.51 (t, J=7.8 Hz, 2H), 7.37 (d, J=8.1 Hz, 1H),5.27 (dd, J=9.3 Hz, 1.2 Hz, 1H), 4.14 (dd, J=15.0 Hz, 1.2 Hz, 1H), 3.86(s, 3H), 3.74 (dd, J=15.0 Hz, 9.3 Hz, 1H), 1.61 (s, 9H).

EXAMPLE 45 (15)5-(2-Ethoxycarbonylethyl)-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2346]

[2347] TLC: Rf 0.28 (ethyl acetate:hexane=1:1);

[2348] NMR (CDCl₃): δ 7.77-7.70 (m, 2H), 7.61 (t, J=7.5 Hz, 1H),7.50-7.35 (m, 4H), 5.19 (dd, J=9.3, 1.8 Hz, 1H), 4.23 (dd, J=15.0, 1.8Hz, 1H), 4.16 (q, J=7.2 Hz, 2H), 3.81 (dd, J=15.0, 9.3 Hz, 1H), 3.80 (s,3H), 3.00-2.87 (m, 2H), 2.65-2.40 (m, 2H), 1.27 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (16)3-Benzylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2349]

[2350] TLC: Rf 0.39 (hexane:ethyl acetate=1:1);

[2351] NMR (CDCl₃): δ 3.89 (dd, J=15.0 Hz, 9.3 Hz, 1H), 3.98 (d, J=14.0Hz, 1H), 4.03 (dd, J=15.0 Hz, 3.6 Hz, 1H), 4.31 (d, J=14.0 Hz, 1H), 4.91(dd, J=9.3, Hz, 3.6 Hz, 1H), 7.21-7.35 (m, 5H), 7.62-7.71 (m, 2H),7.80-7.90 (m, 2H).

EXAMPLE 45 (17)3-(3,4-Dichlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2352]

[2353] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2354] NMR (DMSO-d₆): δ 7.98 (d, J=2.1 Hz, 1H), 7.75-7.89 (m, 5H), 7.63(dd, J=8.4, 2.1 Hz, 1H), 5.91 (dd, J=8.0, 4.4 Hz, 1H), 4.04 (dd, J=15.4,8.0 Hz, 1H), 3.95 (dd, J=15.4, 4.4 Hz,1H).

EXAMPLE 45 (18)3-(4-Nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2355]

[2356] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[2357] NMR (DMSO-d₆): δ 8.41 (d, J=8.8 Hz, 2H), 8.04 (d, J=8.8 Hz, 2H),7.76-7.85 (m, 4H), 5.97 (dd, J=9.0, 3.2 Hz, 1H), 4.04 (dd, J=15.4, 9.0Hz, 1H), 3.90 (dd, J=15.4, 3.2 Hz,1H).

EXAMPLE 45 (19)5-Hydroxymethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2358]

[2359] TLC: Rf 0.51 (ethyl acetate);

[2360] NMR (DMSO-d₆): δ 7.80-7.72 (m, 4H), 7.64-7.51 (m, 3H), 5.66 (dd,J=8.5, 1.5 Hz, 1H), 5.43 (t, J=5.5 Hz, 1H), 4.52 (d, J=5.5 Hz, 1H), 4.13(dd, J=15.0,8.5Hz, 1H), 4.00 (dd, J=15.0, 1.5 Hz, 1H), 3.58 (s, 3H).

EXAMPLE 45 (20)4-Hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2361]

[2362] TLC: Rf 0.54 (chloroform:methanol=9:1);

[2363] NMR (CDCl₃): δ 7.84 (d, J=7.5 Hz, 1H), 7.72-7.63 (m, 2H),7.62-7.53 (m, 3H), 7.51-7.44 (m, 2H), 5.53 (d, J=9.3 Hz, 1H), 5.08 (d,J=13.5 Hz, 1H), 5.01 (d, J=13.5 Hz, 1H), 3.87 (d, J=15.0 Hz, 1H), 3.75(dd, J=15.0, 9.3 Hz, 1H), 3.00-1.80 (br, 1H).

EXAMPLE 45 (21)6-Fluoro-3-phenylsuifonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2364]

[2365] TLC: Rf 0.40 (ethyl acetate:hexane=1:1);

[2366] NMR (DMSO-d₆): δ 7.85-7.58 (m, 8H), 5.77 (dd, J=9.6 Hz, 2.7Hz,1H), 4.07 (dd, J=15.6 Hz, 9.6 Hz, 1H), 3.87 (dd, J=15.6 Hz, 2.7 Hz,1H).

EXAMPLE 45 (22)4-Fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2367]

[2368] TLC: Rf 0.29 (ethyl acetate:hexane=1:1);

[2369] NMR (DMSO-d₆): δ 7.83-7.57 (m, 8H), 5.81 (dd, J=9.0 Hz, 1.5 Hz,1H), 4.09 (dd, J=15.6 Hz, 1.5 Hz, 1H), 3.99 (dd, J=15.6 Hz, 9.0 Hz, 1H).

EXAMPLE 46 5-Methoxycarbonyl-4-ethoxybenzo[b]thiophene

[2370]

[2371] By the same procedure as described in Example 18 using5-methoxycarbonyl-4-hydroxybenzo[b]thiophene instead of the compoundprepared in Example 9 (12) and ethyl iodide instead of4-nitrobenzylbromide, the compound of the present invention having thefollowing physical data was obtained.

[2372] TLC: Rf 0.44 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 7.82 (d,J=8 Hz, 1H), 7.63 (d, J=8 Hz, 1H), 7.54 (d, J=6 Hz, 1H), 7.43 (d, J=6Hz, 1H), 4.21 (q, J=7 Hz, 2H), 3.95 (s, 3H), 1.49 (t, J=7 Hz, 3H).

EXAMPLE 47 5-Carboxy-4-ethoxybenzo[b]thiophene

[2373]

[2374] To the compound prepared in Example 46 (1.11 g), were addedmethanol (10 ml) and a 2N aqueous solution of sodium hydroxide (5.0 ml).The mixture was refluxed for 30 minutes. The reaction mixture wasconcentrated. The residue was acidified by addition of 1 N hydrochloricacid. The mixture was extracted by ethyl acetate. The extract was washedby water and a saturated aqueous solution of sodium chloridesuccessively, dried over anhydrous sodium sulfate and concentrated togive the compound of the present invention (1.02 g) having the followingphysical data.

[2375] TLC: Rf 0.06 (hexane:ethyl acetate 4:1);

[2376] NMR (CDCl₃): δ 8.09 (d, J=8 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.52(d, J=6 Hz, 1H), 7.49 (d, J=6 Hz, 1H), 4.44 (q, J=7 Hz, 2H), 1.58 (t,J=7 Hz, 3H).

EXAMPLE 48 5-Benzyloxycarbonyl-4-ethoxybenzo[b]thiophene

[2377]

[2378] By the same procedure as described in Example 32 using thecompound prepared in Example 47 instead of4-carboxy-1,1-dioxidebenzo[b]thiophene, and benzyl bromide, the compoundhaving the following physical data was obtained.

[2379] TLC: Rf 0.46 (hexane:ethyl acetate=4:1);

[2380] NMR (CDCl₃): δ 7.85 (d, J=8 Hz, 1H), 7.62 (d, J=8 Hz, 1H),7.56-7.26 (m, 7H), 5.40 (s, 2H), 4.15 (q, J=7 Hz, 2H), 1.37 (t, J=7 Hz,3H).

EXAMPLE 49 5-Benzyloxycarbonyl-4-ethoxy-1,1-dioxidebenzo[b]thiophene

[2381]

[2382] By the same procedure as described in 3 using the compoundprepared in Example 48 instead of the compound prepared in Example 1,the compound having the following physical data was obtained (with theproviso that 3-chloroperbenzoic acid was used instead of OXONE™ as anoxidizer).

[2383] TLC: Rf 0.10 (hexane:ethyl acetate=4:1);

[2384] NMR (CDCl₃): δ 7.99 (d, J=8 Hz, 1H), 7.60-7.30 (m, 7H), 6.72 (d,J=7 Hz, 1H), 5.38 (s, 2H) 4.03 (q, J=7 Hz, 2H), 131 (t, J=7 Hz, 3H.

EXAMPLES 50˜50 (2)

[2385] By the same procedure as described in Example 46→Example47→Example 48→Example 49 using a corresponding halide compound insteadof ethyl iodide, the following compounds of the present invention wereobtained.

EXAMPLE 50 5-Benzyloxycarbonyl-4-hexyloxy-1,1-dioxidebenzo[b]thiophene

[2386]

[2387] TLC: Rf 0.22 (hexane:ethyl acetate=4:1); (s, 2H), 3.93 (t, J=7Hz, 2H), 7.55-7.30 (m, 7H), 6.72 (d, J=7 Hz, 1H), 5.38 (s, 2H), 3.93 (t,J=7 Hz, 2H), 1.80-1.45 (m, 2H), 1.45-1.10 (m, 6H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 50 (1) 5-Benzyloxycarbonyl-4-butoxy-1,1-dioxidebenzo[b]thiophene

[2388]

[2389] TLC: Rf 0.24 (hexane:ethyl acetate=4:1);

[2390] NMR (CDCl₃): δ 7.98 (d, J=8 Hz, 1H), 7.58-7.38 (m, 7H), 6.72 (d,J=7 Hz, 1H), 5.33 (s, 2H), 3.94 (t, J=7 Hz, 2H), 1.78-1.50 (m, 2H),1.50-1.20 (m, 2H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 50 (2)5-Benzyloxycarbonyl-4-octyloxy-1,1-dioxidebenzo[b]thiophene

[2391]

[2392] TLC: Rf 0.33 (hexane:ethyl acetate=4:1);

[2393] NMR (CDCl₃): δ 7.97 (d, J=8 Hz, 1H), 7.60-7.25 (m, 7H), 6.72 (d,J=7 Hz, 1H), 5.38 (s, 2H), 3.92 (t, J=7 Hz, 2H), 1.82-1.45 (m, 2H),1.45-1.05 (m, 10H), 0.89 (t, J=7 Hz, 3H).

EXAMPLES 51˜51 (3)

[2394] By the same procedure as described in Example 27 using thecompounds prepared in Example 49 and Examples 50˜50 (2) instead of5-methyl-1,1-dioxidebenzo[b]thiophene, the following compounds of thepresent invention were obtained.

EXAMPLE 515-Benzyloxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2395]

[2396] TLC: Rf 0.41 (chloroform hexane:methanol=5:5:1);

[2397] NMR (CDCl₃): δ 7.90 (d, J=8 Hz, 1H), 7.78-7.66 (m, 2H), 7.64-7.30(m, 9H), 5.34 (s, 2H), 5.17 (d, J=9 Hz, 1H), 4.30 (dd, J=1, 15 Hz, 1H),4.10-3.60 (m, 3H), 1.13 (t, J=7 Hz, 3H).

EXAMPLE 51 (1)5-benzyloxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2398]

[2399] TLC: Rf 0.45 (chloroform:hexane:methanol=5:5:1);

[2400] NMR (CDCl₃): δ 7.88 (d, J=8 Hz, 1H), 7.78-7.64 (m, 2H), 7.60-7.28(m, 9H), 5.34 (s, 2H), 5.15 (d, J=9 Hz, 1H), 4.32 (dd, J=1, 15 Hz, 1H),4.00-3.46 (m, 3H), 1.75-1.05 (m, 8H), 0.91 (t, J=7 Hz, 3H).

EXAMPLE 51 (2)5-Benzyloxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2401]

[2402] TLC: Rf 0.43 (chloroform:hexane:methanol=5:5:1);

[2403] NMR (CDCl₃): δ 7.88 (d, J=8 Hz, 1H), 7.78-7.64 (m, 2H), 7.60-7.28(m, 9H), 5.34 (s, 2H), 5.15 (d, J=9 Hz, 1H), 4.32 (dd, J=1, 15 Hz, 1H),4.02-3.48 (m, 3H), 1.70-1.10 (m, 4H), 0.87 (t, J=7 Hz, 3H).

EXAMPLE 51 (3)5-Benzyloxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2404]

[2405] TLC: Rf 0.47 (chloroform:hexane:methanol=5:5:1);

[2406] NMR (CDCl₃): δ 7.88 (d, J=8 Hz, 1H), 7.76-7.64 (m, 2H), 7.60-7.26(m, 9H), 5.34 (s, 2H), 5.15 (d, J=9 Hz, 1H), 4.32 (dd, J=1, 15 Hz, 1H),4.00-3.46 (m, 3H), 1.75-1.05 (m, 12H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 525-Carboxy-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2407]

[2408] To a solution of the compound prepared in Example 51 (670 mg) inethyl acetate (50 ml). Thereto was added 10% palladium carbon (220 mg).Under an atmosphere of hydrogen the mixture was stirred at roomtemperature for 2 hours. The reaction mixture was filtered throughcelite. The filtrate was washed by ethyl acetate and concentrated. Theresidue was dissolved in ethyl acetate under heating and wasrecrystallized by addition of hexane (5 ml). The crystal was separatedby filtration and dried to give the compound of the present invention(471 mg) having the following physical data.

[2409] TLC: Rf 0.21 (chloroform:acetic acid=10:1);

[2410] NMR (CDCl₃+acetone-d₆): δ 8.02 (d, J=8 Hz, 1H), 7.86-7.72 (m,2H), 7.72-7.58 (m, 1H), 7.58-7.32 (m, 3H), 5.33 (d, J=9 Hz, 1H), 4.30(d, J=15 Hz, 1H), 4.24-4.06 (m, 1H), 4.20 (bs, 1H), 4.02-3. 74 (m, 2H),1.25 (t, J=7 Hz, 3H).

EXAMPLES 52 (1)˜52 (3)

[2411] By the same procedure as described in Example 52 using thecompounds prepared in Examples 51 (1)˜51 (3) instead of Example 51, thefollowing compounds were obtained.

EXAMPLE 52 (1)5-Carboxy-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2412]

[2413] TLC: Rf 0.38 (chloroform:acetic acid=10:1);

[2414] NMR (CDCl₃+acetone-d₆): δ 8.00 (d, J=8 Hz, 1H), 7.88-7.72 (m,2H), 7.72-7.56 (m, 1H), 7.56-7.34 (m, 3H), 5.32 (d, J=9 Hz,1H), 4.31(dd, J=1, 15 Hz, 1H), 4.20 (brs, H), 4.14 (dt, J=7, 9 Hz, 1H), 4.02-3.66(m, 2H), 1.80-1.45 (m, 2H), 1.45-1.12 (m, 6H), 0.91 (t, J=7 Hz, 3H).

EXAMPLE 52 (2)5-Carboxy-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2415]

[2416] TLC: Rf 0.34 (chloroform:acetic acid=10:1);

[2417] NMR (CDCl₃+acetone-d₆): δ 8.00 (d, J=8 Hz, 1H), 7.86-7.72 (m,2H), 7.72-7.56 (m, 1H), 7.56-7.34 (m, 3H), 5.32 (d, J=9 Hz,1H), 4.31(dd, J=1, 15 Hz, 1H), 4.20 (brs, 1H), 4.15 (dt, J=7,9 Hz, 1H), 4.00-3.66(m, 2H), 1.74-1.48 (m, 2H), 1.48-1.20 (m, 2H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 52 (3)5-Carboxy-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2418]

[2419] TLC: Rf 0.40 (chloroform:acetic acid 10:1);

[2420] NMR (CDCl₃+acetone-d₆): δ 8.00 (d, J=8 Hz, 1H), 7.84-7.72 (m,2H), 7.72-7.57 (m, 1H), 7.57-7.34 (m, 3H), 5.33 (d, J=9 Hz, 1H), 4.31(dd, J=1, 15 Hz, 1H), 4.13 (dt, J=7, 9 Hz, 1H), 4.10 (brs,1 H ),4.00-3.66 (m, 2H), 1.74-1.43 (m, 2H), 1.43-1.05 (m, 10H), 0.90 (t, J=7Hz, 3H).

EXAMPLES 53˜53 (3)

[2421] By the same procedure as described in Example 32 using thecompounds prepared in Examples 52˜52 (3) instead of 4-hydroxy1,1-dioxidebenzo[b]thiophene and corresponding alcohol derivativesinstead of 1-(3-hydroxypropyl)pyrrole, the following compounds of thepresent invention were obtained.

EXAMPLE 535-Methoxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2422]

[2423] TLC: Rf 0.35 (chloroform:hexane:methanol=5:5:1);

[2424] NMR (CDCl₃): δ 6 7.91 (d, J=8 Hz, 1H), 7.84-7.72 (m, 2H),7.72-7.57 (m, 1H), 7.57-7.32 (m, 3H), 5.21 (d, J=9 Hz,1H), 4.28 (dd,J=1,15 Hz,1H), 4.20-4.00 (m, 1H), 3.93 (s, 3H), 3.95-3.68 (m, 2H), 1.26(t, J=7 Hz, 3H).

EXAMPLE 53 (1)5-Methoxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2425]

[2426] TLC: Rf 0.42 (chloroform:hexane:methanol=5:5:1);

[2427] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.82-7.69 (m, 2H), 7.69-7.55(m, 1H), 7.55-7.30 (m, 3H), 5.19 (d, J=9 Hz, 1H), 4.30 (d, J=15 Hz, 1H),4.08 (dt, J=7, 9 Hz, 1H), 3.93 (s, 3H), 3.95-3.55 (m, 2H), 1.80-1.46 (m,2H), 1.46-1.15 (m, 6H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 53 (2)5-Methoxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2428]

[2429] TLC: Rf 0.37 (chloroform:hexane:methanol=5:5:1);

[2430] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.82-7.68 (m, 2H), 7.68-7.55(m, 1H), 7.55-7.34 (m, 3H), 5.19 (d, J=9 Hz, 1H), 4.31 (dd, J=1, 15 Hz,1H), 4.05 (dt, J=7, 9 Hz, 1H), 3.93 (s, 3H), 3.88-3.60 (m, 2H),1.80-1.50 (m, 2H), 1.50-1.18 (m, 2H), 0.94 (t, J=7 Hz, 3H).

EXAMPLE 53 (3)5-Methoxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2431]

[2432] TLC: Rf 0.44 (chloroform:hexane:methanol=5:5:1);

[2433] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.80-7.69 (m, 2H), 7.69-7.55(m, 1H), 7.55-7.34 (m, 3H), 5.19 (d, J=9 Hz, 1H), 4.30 (dd, J=1,15 Hz,1H), 4.06 (dt, J=7, 9 Hz, 1H), 3.93 (s, 3H), 3.90-3.58 (m, 2H),1.80-1.45 (m, 2H), 1.45-1.10 (m, 10H), 0.90 (t, J=7 Hz, 3H).

EXAMPLES 54˜54 (19)

[2434] By the same procedure as described in Example 28 using thecompounds prepared in Examples 52˜52 (3) instead of4-carboxy-1,1-dioxidebenzo[b]thiophene and amine derivativescorresponding to (pyridin-3-ylmethyl)amine, the following compounds ofthe present invention were obtained.

EXAMPLE 54 5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2435]

[2436] TLC: Rf 0.73 (chloroform:methanol=5:1);

[2437] NMR (CDCl₃): δ 7.90 (d, J=8 Hz, 1H), 7.78-7.15 (m, 10H), 5.33 and5.19 (each d, J=9 Hz, total 1H), 4.40-3.50 (m, 6H), 3.40-2.25 (m, 10H),1.30-1.10 (m, 3H).

EXAMPLE 54 (1)5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2438]

[2439] TLC: Rf 0.75 (chloroform:methanol=5:1);

[2440] NMR (CDCl₃): δ 7.90 (d, J=8 Hz, 1H), 7.80-6.85 (m, 10H), 5.33 and5.21 (each d, J=9 Hz, total 1H), 4.45-3.55 (m, 6H), 3.50-2.80 (m, 6H),1.25 (t, J=7 Hz, 3H).

EXAMPLE 54 (2)5-(2-Dimethylaminoethyl)carbamoyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2441]

[2442] TLC: Rf 0.34 (chloroform:methanol 5:1);

[2443] NMR (CDCl₃): δ 8.24 and 8.11 (each d, J=8 Hz, total 1H),8.00-7.15 (m, 7H), 5.15 (d, J=9 Hz, 1H), 4.50-3.30 (m, 6H), 2.54 (t, J=7Hz, 2H), 2.32 (s, 6H), 1.45-1.20 (m, 3H).

EXAMPLE 54 (3)5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2444]

[2445] TLC: Rf 0.19 (ethyl acetate:hexane=2:1);

[2446] NMR (CDCl₃): δ 7.87 (d, J=8 Hz, 1H), 7.80-7.20 (m, 6H), 5.32 and5.20 (each d, J=9 Hz, total 1H), 4.40-2.90 (m, 8H), 2.10-1.00 (m, 11H).

EXAMPLE 54 (4)5-(2,3-Dihydroindol-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2447]

[2448] TLC: Rf 0.40 (ethyl acetate:hexane=2:1);

[2449] NMR (CDCl₃): δ 8.29 (d, J=8 Hz, 1H), 8.05-6.90 (m, 10H),5.38-5.10 (m, 1H), 4.50-3.40 (m, 6H), 3.16 (t, J=8 Hz, 2H), 1.40-1.00(m, 3H).

EXAMPLE 54 (5)5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2450]

[2451] TLC: Rf 0.57 (chloroform:methanol=10:1);

[2452] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.76-7.20 (m, 10H), 5.30 and5.17 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.20-3.50 (m,5H), 3.50-2.80 (m, 4H), 280-2.20 (m, 6H), 1.90-1.05 (m, 8H), 0.90 (t,J=7 Hz, 3H).

EXAMPLE 54 (6)5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2453]

[2454] TLC: Rf 0.66 (chloroform:methanol 10:1);

[2455] NMR (DMSO-d₆): δ 8.31 (s, 1H), 8.00-6.95 (m, 10H), 5.66 (d, J=9Hz, 1H), 4.32 (d, J=15 Hz, 1H), 4.22-2.70 (m, 11H), 1.60-1.02 (m, 8H),0.87 (t, J=7 Hz, 3H).

EXAMPLE 54 (7)5-(2-Dimethylaminoethyl)carbamoyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2456]

[2457] TLC: Rf 0.23 (chloroform:methanol=10:1);

[2458] NMR (CDCl₃): δ 8.21 and 8.07 (each d, J=8 Hz, total 1H),7.90-7.10 (m, 7H), 5.13 (d, J=9 Hz,1H), 4.32 (d, J=15 Hz, 1H), 4.25-3.35(m, 5H), 2.56 and 2.57 (each t, J=6 Hz, total 2H), 2.33 (s, 6H),2.05-1.10 (m, 8H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 54 (8)5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2459]

[2460] TLC: Rf 0.23 (hexane:ethyl acetate 1:1);

[2461] NMR (CDCl₃): δ 7.86 (d, J=8 Hz, 1lH), 7.78-7.20 (m, 6H), 5.30 and5.18 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.35-3.00 (m,7H), 2.10-1.10 (m, 16H), 0.91 (t, J=7 Hz, 3H).

EXAMPLE 54 (9)5-(2,3-Dihydroindol-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2462]

[2463] TLC: Rf 0.39 (hexane:ethyl acetate=1:1);

[2464] NMR (CDCl₃) δ 8.29 (d, J=8 Hz, 1H), 8.10-6.80 (m, lIOH),5.40-5.05 (m, 1H), 4.50-3.35 (m, 6H), 3.16 (t, J=8 Hz, 2H), 1.90-0.95(m, 8H), 0.95-0.75 (m, 3H).

EXAMPLE 54 (10)5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2465]

[2466] TLC: Rf 0.56 (chloroform:methanol=10:1);

[2467] NMR (CDCl₃): δ7.88 (d, J=8 Hz, 1H), 7.80-7.00 (m, 10H), 5.30 and5.18 (each d, J=9 Hz, total 1H), 4.40-3.45 (m, 6H), 3.45-2.80 (m, 4H),2.80-2.15 (m, 6H), 2.00-1.10 (m, 4H), 0.97 and 0.91 (each t, J=7 Hz,total 3H).

EXAMPLE 54 (11)5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2468]

[2469] TLC: Rf 0.65 (chloroform:methanol=10:1);

[2470] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.80-7.17 (m, 8H), 7.17-6.85(m, 2H), 5.31 and 5.19 (each d, J=9 Hz, total 1H), 4.40-3.55 (m, 6H),3.55-2.70 (m, 6H), 2.00-1.15 (m, 4H), 0.99 and 0.94 (each t, J=7 Hz,total 3H).

EXAMPLE 54 (12) 5-(2-Dimethylamino ethyl)carbamoyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2471]

[2472] TLC: Rf 0.21 (chloroform:methanol=10:1);

[2473] NMR (CDCl₃): δ 8.08 (d, J=8 Hz, 1H), 7.85-7.35 (m, 6H), 7.25(broad peak, 1H), 5.13 (d, J=9 Hz, 1H), 4.32 (d, J=15 Hz, 1H), 4.05-3.66(m, 3H), 3.66-3.35 (m, 2H), 2.52 (t, J=7 Hz, 2H), 2.3 1 (s, 6H),1.90-1.15 (m, 4H), 0.96 (t, J=7 Hz, 3H).

EXAMPLE 54 (13)5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2474]

[2475] TLC: Rf 0.19 (ethyl acetate:hexane=1:1);

[2476] NMR (CDCl₃). δ 7.85 (d, J=8 Hz, 1H), 7.76-7.20 (m, 6H), 5.29 and5.18 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.25-3.60 (m,4H), 3.60-3.00 (m, 3H), 2.10-1.10 (m, 12H), 0.96 and 0.92 (each t, J=7Hz, total 3H).

EXAMPLE 54 (14)5-(2,3-Dihydroindol-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2477]

[2478] TLC: Rf 0.31 (ethyl acetate:hexane=1:1);

[2479] NMR (CDCl₃): δ 8.29 (d, J=8 Hz, 1H), 8.05-7.42 (m, 6H), 7.42-6.95(m, 4H), 5.36-5.06 (m, 1H), 4.50-3.40 (m, 6H), 3.16 (t, J=7 Hz),1.90-1.05 (m, 4H), 0.81 (t, J=7 Hz, 3H).

EXAMPLE 54 (15)5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2480]

[2481] TLC: Rf 0.66 (chloroform:methanol=10:1);

[2482] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.80-7.20 (m, 10H), 5.30 and5.17 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.30-3.55 (m,5H), 3.55-2.80 (m, 4H), 2.80-2.25 (m, 6H), 1.90-1.05 (m, 12H), 0.88 (t,J=7 Hz, 3H).

EXAMPLE 54 (16)

[2483]5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2484] TLC: Rf 0.74 (chloroform:methanol 10:1);

[2485] NMR (CDCl₃): δ 7.89 (d, J=8 Hz, 1H), 7.82-6.85 (m, 10H), 5.31 and5.19 (each d, J=9 Hz, total 1H), 4.38-2.70 (m, 12H), 1.90-1.05 (m, 12H),0.89 (t, J=7 Hz, 3H).

EXAMPLE 54 (17)5-(2-Dimethylaminoethyl)carbamoyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2486]

[2487] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2488] NMR (CDCl₃): δ 7.99 (d, J=8 Hz, 1H), 7.92-7.10 (m, 7H), 5.30-5.00(m, 1H), 4.40-3.45 (m, 6H), 2.70 (t, J=6 Hz, 2H), 2.46 (s, 6H),1.95-1.05 (m, 12H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 54 (18)5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2489]

[2490] TLC: Rf 0.26 (hexane:ethyl acetate 1:1);

[2491] NMR (CDCl₃): δ 7.85 (d, J=8 Hz, 1H), 7.88-7.15 (m, 6H), 5.29 and5.18 (each d, J=9 Hz, total 1H), 4.40-3.00 (m, 8H), 2.10-1.05 (m, 20H),0.90 (t, J=7 Hz, 3H).

EXAMPLE 54 (19)5-(2,3-Dihydroindol-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2492]

[2493] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2494] NMR (CDCl₃): δ 8.29 (d, J=8 Hz, 1H), 8.10-6.80 (m, 10H),5.40-5.05 (m, 1H), 4.60-3.40 (m, 6H), 3.16 (t, J=8 Hz, 2H), 1.90-1.00(m, 12H), 0.85 (t, J=7 Hz, 3H).

EXAMPLE 55 5-Hydroxy-4-formylbenzo[b]thiophene

[2495]

[2496] To a solution of 5-hydroxybenzo[b]thiophene (3.0 g) in methylenechloride (60 ml), were added at 0° C. dichloromethyl methyl ether (4.52ml) and titanium tetrachloride (5.48 ml) dropwise. The mixture wasstirred at room temperature for 30 minutes. The reaction mixture waspoured onto ice-water. The mixture was extracted by ethyl acetate. Theextract was washed by a saturated aqueous solution of sodium chloride,dried over anhydrous magnesium sulfate and concentrated. The residue waspurified with column chromatography on silica gel (methylene chloride)to give the compound of the present invention (1.50 g) having thefollowing physical data.

[2497] TLC: Rf 0.69 (hexane:ethyl acetate=2:1);

[2498] NMR (CDCl₃): δ 11.97 (s, 1H), 10.55 (s, 1H), 7.96 (d, J=8.8 Hz,1H), 7.77 (d, J=5.6 Hz, 1H), 7.72 (d, J=5.6 Hz, 1H), 7.02 (d, J=8.8 Hz,1H).

EXAMPLE 56 5-Benzyloxy-4-formylbenzo[b]thiophene

[2499]

[2500] By the same procedure as described in Example 18 using thecompound prepared in Example 55 instead of the compound prepared inExample 9 (12) and benzylbromide instead of 4-nitrobenzylbromide, thecompound of the present invention having the following physical data wasobtained.

[2501] TLC: Rf 0.65 (hexane:ethyl acetate=2:1);

[2502] NMR (CDCl₃): δ 10.81 (s, 1H), 8.43 (d, J=5.6 Hz, 1H), 8.00 (d,J=8.8 Hz, 1H), 7.68 (d, J=5.6 Hz, 1H), 7.55-7.30 (m, 5H), 7.15 (d, J=8.8Hz, 1H), 5.28 (s, 2H).

EXAMPLE 57 5-Benzyloxy-4-hydroxymethylbenzo[b]thiophene

[2503]

[2504] To a solution of the compound prepared in Example 56 (1.24 g) inmethylene chloride (9.0 ml), were added sodium borohydride (246 mg) andmethanol, (3.0 ml). The mixture was stirred at room temperature for 30minutes. The reaction mixture was poured onto 1 N hydrochloric acid andwas extracted by ethyl acetate. The extract was washed by a saturatedaqueous solution of sodium chloride, dried over anhydrous magnesiumsulfate and concentrated. The residue was purified with chromatographyon silica gel (hexane:ethyl acetate=4:1) to give the compound of thepresent invention (1.25 g) having the following physical data.

[2505] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[2506] NMR (CDCl₃): δ 7.76 (d, J=8.8 Hz, 1H), 7.54-7.28 (m, 7H), 7.12(d, J=8.8 Hz, 1H), 5.20 (s, 2H), 5.04 (br-s, 2H), 2.30-2.12 (br, 1H).

EXAMPLE 58 5-Benzyloxy-4-hydroxymethyl-1,1-dioxidebenzo[b]thiophene

[2507]

[2508] By the same procedure as described in Example 3 using thecompound prepared in Example 57 instead of the compound prepared inExample 1, the compound having the following physical data was obtained(with the proviso that 3-chloroperbenzoic acid was used instead ofOXONE@ as an oxidizer.).

[2509] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2510] NMR (CDCl₃): δ 7.61 (d, J=7.0 Hz,1H), 7.56 (d, J=7.0 Hz, 1H),7.48-7.34 (m, 5H), 7.02 (d, J=8.4 Hz, 1H), 6.75 (d, J=7.0 Hz, 1H), 5.18(s, 2H), 4.84 (brs, 2H), 2.26-2.10 (br, 1H).

EXAMPLE 595-Benzyloxy-4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2511]

[2512] By the same procedure as described in Example 1 using thecompound prepared in Example 58 instead of 1,1-dioxidebenzo[b]thiophene,and thiophenol, the compound of the present invention having thefollowing physical data was obtained.

[2513] TLC: Rf 0.60 (chloroform:ethyl acetate=19:1);

[2514] NMR (CDCl₃): δ 7.67 (d, J=8.4 Hz, 1H), 7.57-7.48 (m, 2H),7.46-7.32 (m, 8H), 7.15, (d, J=8.4 Hz, 1H), 5.24 (s, 2H), 5.19 (dd,J=6.6, 1.8 Hz, 1H), 4.99 (d, J=6.0 Hz, 2H), 3.71 (dd, J=14.0, 6.6 Hz,1H), 3.59 (dd, J=14.0, 1.8 Hz, 1H), 2.59 (t, J=6.0 Hz,1H).

EXAMPLE 605-Benzyloxy-4-bromomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenz[b]thiophene

[2515]

[2516] To a solution of the compound prepared in Example 59 (1.45 g) inmethylene chloride (15 ml), was added triphenylphosphine (1.38 g) andcarbon tetrabromide (1.74 g). The mixture was stirred at roomtemperature for 30 minutes. The reaction mixture was concentrated. Theresidue was purified with column chromatography on silica gel(hexane:ethyl acetate=2:1) to give the compound of the present inventionhaving the following physical data.

[2517] TLC: Rf 0.76 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.66 (d,J=8.8 Hz, 1H), 7.60-7.51 (m, 2H), 7.50-7.30 (m, 8H), 7.12 (d, J=8.8 Hz,1H), 5.27 (s, 2H), 5.15 (dd, J=6.8, 1.6 Hz, 1H), 5.02 (d, J=10 Hz, 1H),4.94 (d, J=10 Hz, 1H), 3.74 (dd, J=13.8, 6.8 Hz, 1H), 3.60 (dd,J=13.8,1.6 Hz, 1H).

EXAMPLE 615-Benzyloxy-4-aminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2518]

[2519] To a solution of 28% aqueous ammonia solution (6.75 ml) intetrahydrofuran (30 ml), were added a solution of the compound preparedin Example 60 (1.60 g) in tetrahydrofuran (30 ml) and potassiumcarbonate (700 mg) successively. The mixture was stirred at roomtemperature for 1.5 hours. The reaction mixture was concentrated. Theresidue was purified with column chromatography on silica gel(chloroform:methanol=20:1) to give the compound of the present invention(747 mg) having the following physical data.

[2520] TLC: Rf 0.05 (hexane:ethyl acetate=1:1);

[2521] NMR (CDCl₃): δ 7.63 (d, J=8.5 Hz, 1H), 7.58-7.48 (m, 2H),7.46-7.28 (m, 8H), 7.14 (d, J=8.5 Hz, 1H), 5.23 (s, 2H), 5.13 (dd,J=6.4, 1.6 Hz, 1H), 4.12 (d, J=13.6 Hz, 1H), 4.02 (d, J=13.6 Hz, 1H),3.70 (dd, J=14.0, 6.0 Hz, 1H), 3.59 (dd, J=14.0, 1.6 Hz, 1H).

EXAMPLE 625-Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2522]

[2523] To the solution of the compound prepared in Example 61 (735 mg)in tetrahydrofuran (12 ml) and water (3.0 ml), were added sodiumbicarbonate (165 mg) and di-t-butyldicarbonate (430 mg) at 0° C. Themixture was stirred at room temperature for 1 hour. The reaction mixturewas poured onto water and was extracted by ethyl acetate. The extractwas washed by a saturated aqueous solution of sodium chloride, driedover anhydrous magnesium sulfate and concentrated. The residue waspurified with column chromatography on silica gel (hexane:ethylacetate=2:1) to give the compound of the present invention (867 mg)having the following physical data.

[2524] TLC: Rf 0.73 (hexane:ethyl acetate=1:1);

[2525] NMR (CDCl₃): δ 7.70-7.56 (m, 3H), 7.48-7.30 (m, 8H), 7.12 (d,J=8.8 Hz, 1H), 5.66 (br-d, J=5.8 Hz, 1H), 5.22 (s, 2H), 5.20-4.88 (m,2H), 4.25-4.10 (m, 1H), 3.71 (dd, J=14.0, 6.8 Hz, 1H), 3.56 (d, J=14.0Hz, 1H), 1.41 (s, 9H).

EXAMPLE 635-Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2526]

[2527] By the same procedure as described in Example 3 using thecompound prepared in Example 62 instead of the compound prepared inExample 1, the compound of the present invention having the followingphysical data (with the proviso that 3-chloroperbenzoic acid was usedinstead of OXONE@ as an oxidizer.).

[2528] TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

[2529] NMR (CDCl₃): δ 7.83-7.76 (m, 2H), 7.71-7.64 (m, 1H), 7.60 (d,J=8.7 Hz, 1H), 7.56-7.38 (m, 7H), 7.19 (d, J=8.7 Hz, 1H), 6.05 (brd,J=6.9 Hz, 1H), 5.27-5.15 (m, 1H), 5.25 (s, 2H), 5.10-4.95 (m, 1H),4.27-4.16 (m, 1H), 3.81 (dd, J=15.3, 2.1 Hz, 1H), 3.74 (dd, J=15.3, 8.1,1H), 1.37 (s, 9H).

EXAMPLE 645-Benzyloxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[2530]

[2531] By the same procedure as described in Example 7 using thecompound prepared in Example 63 instead of the compound prepared inExample 6 (8), the compound of the present invention having thefollowing physical data was obtained.

[2532] TLC: Rf 0.43 (chloroform:methanol=9:1);

[2533] NMR (DMSO-d₆): δ 8.18 (brs, 3H), 7.86 (d, J=9.0 Hz, 1H),7.83-7.75 (m, 3H), 7.67-7.48 (m, 5H), 7.47-7.33 (m, 3H), 6.37 (dd,J=6.0, 3.9 Hz, 1H), 5.41 (d, J=12.3 Hz, 1H), 5.33 (d, J=12.3 Hz, 1H),4.44 (d, J=13.8 Hz, 1H), 4.24 (d, J=13.8 Hz, 1H), 3.90-3.76 (m, 2H).

EXAMPLE 65 5-Hydroxy-4-t-butoxycarbonylaminoethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2534]

[2535] By the same procedure as described in Example 52 using thecompound prepared in Example 63 instead of the compound prepared inExample 51, the compound of the present invention having the followingphysical data was obtained.

[2536] TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

[2537] NMR (CDCl₃): δ 10.75 (s, 1H), 7.75-7.58 (m, 3H), 7.56-7.41 (m,3H), 7.18 (d, J=8.6 Hz, 1H), 6.35-6.50 (m, 1H), 5.24-5.15 (m, 1H),4.76-4.60 (m, 1H), 4.34 (dd, J=16.0, 5.4 Hz,1H), 3.86-3.66 (m, 2H), 1.37(s, 9H).

EXAMPLES 66˜66 (1)

[2538] By the same procedure as described in Example 29 using thecompound prepared in Example 65 instead of4-hydroxy-1,1-dioxidebenzo[b)thiophene and alcohol derivativescorresponding to 1-(3-hydroxypropyl)pyrrole, the following compounds ofthe present invention were obtained.

EXAMPLE 665-Methoxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2539]

[2540] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[2541] NMR (CDCl₃): δ 7.86-7.75 (m, 2H), 7.74-7.47 (m, 4H), 7.14 (d,J=8.8 Hz, 1H), 6.10-6.00 (m, 1H), 5.32-5.18 (m, 1H), 5.10-4.92 (m, 1H),4.25-4.10 (m, 1H), 4.00 (s, 3H), 3.85-3.65 (m, 2H), 1.38 (s, 9H).

EXAMPLE 66 (1) 5-(3-Phenylpropyl)oxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2542]

[2543] TLC: Rf 0.51 (hexane:ethyl acetate=1:1);

[2544] NMR (CDCl₃): δ 7.87-7.73 (m, 2H), 7.73-7.40 (m, 6H), 7.40-7.16(m, 3H), 7.07 (d, J=8.8 Hz, 1H), 6.55-6.30 (br, 1H), 6.07-5.95 (m, 1H),5.26-5.12 (m, 1H), 5.10-4.90 (m, 1H), 4.20-4.05 (m, 2H), 3.86-3.64 (m,2H), 2.86 (t, J=7.0 Hz, 2H), 2.33-2.15 (m, 2H), 1.38 (s, 9H).

EXAMPLES 67˜67(1)

[2545] By the same procedure as described in Example 7 using thecompounds prepared in Examples 66˜66 (1) instead of the compoundprepared in Example 6 (8), the following compounds of the presentinvention were obtained.

EXAMPLE 675-Methoxy-4-aminomethyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2546]

[2547] TLC: Rf 0.19 (chloroform:methanol=4:1);

[2548] NMR (DMSO-d₆): δ 8.19 (brs, 3H), 7.89-7.76 (m, 4H), 7.68-7.60 (m,2H), 7.47 (d, J=8.7 Hz, 1H), 6.39 (t, J=5.4 Hz, 1H), 4.47-4.28 (br, 1H),4.25-4.08 (br, 1H), 3.98 (s, 3H), 3.82 (d, J=5.4 Hz, 2H).

EXAMPLE 67 (1)5-(3-Phenylpropyl)oxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thibphene.hydrochloride

[2549]

[2550] TLC: Rf 0.43 (chloroform:methanol=9:1);

[2551] NMR (DMSO-d₆): δ 8.14 (brs, 3H), 7.86-7.76 (m, 4H), 7.68-7.61 (m,2H), 7.45 (d, J=8.7 Hz, 1H), 7.34-7.27 (m, 4H), 7.25-7.15 (m, 1H),6.45-6.34 (m, 1H), 4.47-4.13 (m, 4H), 3.89-3.75 (m, 2H), 2.86-2.73 (m,2H), 2.22-2.08 (m, 2H).

EXAMPLE 685-Benzyloxy-4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2552]

[2553] By the same procedure as described in Example 3 using thecompound prepared in Example 59 instead of the compound prepared inExample 1 the compound of the present invention having the followingphysical data was obtained (with the proviso that 3-chloroperbenzoicacid was used instead of OXONE@ as an oxidizer).

[2554] TLC: Rf 0.25 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.72-7.58(m, 3H), 7.56-7.30 (m, 8H), 7.20 (d, J=8.8 Hz, 1H), 5.53 (dd,J=8.4,1.8Hz, 1H), 5.33 (d, J=11.8 Hz, 1H), 5.25 (d, J=11.8 Hz, 1H),5.10-5.01 (m, 2H), 3.87 (dd, J=15.4,1.8 Hz, 1H), 3.75 (dd, J=15.4,1.8Hz, 1H), 3.40-3.28 (m, 1H).

EXAMPLE 695-Benzyoxy-4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2555]

[2556] To a solution of the compound prepared in Example 68 (444 mg) inmethylene chloride (10 ml) were added pyridinium dichromate (564 mg) andmagnesium sulfate (500 mg). The mixture was stirred at room temperaturefor 6 hours. The undissolved ingredients were filtered off. The filtratewas poured onto 1 N hydrochloric acid and was extracted by methylenechloride. The extract was washed by a saturated aqueous solution ofsodium chloride, dried over anhydrous magnesium sulfate andconcentrated. The residue was washed by methanol and was dried. Theobtained solid was dissolved in dimethylformamide (16 ml) and water (4.0ml). Thereto, were added 2-methyl-2-butene (0.48 ml), sodium phosphatebishydrate (120 mg) and sodium hypochloric acid (358 mg). The mixturewas stirred at room temperature for 1 hour. The reaction mixture waspoured onto 0.5 N hydrochloric acid and was extracted by ethyl acetate.The extract was concentrated. The residue was washed by ether to givethe compound of the present invention (305 mg) having the followingphysical data.

[2557] TLC: Rf 0.17 (chloroform:methanol=9:1);

[2558] NMR (DMSO-d₆): δ 13.52 (s, 1H), 7.92-7.68 (m, 4H), 7.67-7.30 (m,8H), 5.88 (d, J 9.0 Hz, 1H), 5.37 (s, 2H), 4.09 (dd, J=15.0, 9.0 Hz,1H), 3.88 (d, J=15.0 Hz, 1H).

EXAMPLE 70 5-Benzyloxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2559]

[2560] By the same procedure as described in Example 28 using thecompound prepared in Example 69 instead of4-carboxy-1,1-dioxidebenzo[b]thiophene, and (pyridin-3-ylmethyl)amine,the compound of the present invention having the following physical datawas obtained.

[2561] TLC: Rf 0.53 (chloroform:methanol=9:1);

[2562] NMR (DMSO-d6): δ 9.05 (t, J=6.0 Hz, 1H), 8.59 (d, J=1.5 Hz, 1H),8.41 (dd, J=4.8, 1.5 Hz,1H), 7.85 (d, J=8.7 Hz, 1H), 7.80-7.72 (m, 3H),7.65-7.55 (m, 4H), 7.48-7.41 (m, 2H), 7.38-7.30 (m, 3H), 7.15 (dd,J=8.1, 4.8 Hz, 1H), 5.96 (d, J=9.0 Hz, 1H), 5.29 (s, 2H), 4.63 (dd,J=15.0, 6.0 Hz,1H), 4.35 (dd, J=15.0, 6.0 Hz, 1H), 4.06 (dd, J=15.0,9.0Hz, 1H), 3.87 (d, J=15.0 Hz, 1H).

EXAMPLE 715-Hydroxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2563]

[2564] By the same procedure as described in Example 52 using thecompound prepared in Example 70 instead of the compound prepared inExample 51, the compound of the present invention having the followingphysical data was obtained.

[2565] TLC: Rf 0.29 (chloroform:methanol=9:1);

[2566] NMR (DMSO-d₆): δ 11.70 (br, 1H), 9.10-8.90 (br, 1H), 8.66 (d,1H), 8.44 (dd, 1H), 7.88-7.81 (m, 1H), 7.78-7.68 (m, 3H), 7.67-7.54 (m,3H), 7.34 (dd, J=7.5, 4.8 Hz, 1H), 7.23 (d, J=8.7 Hz,1H), 6.14 (d, J=9.0Hz, 1H), 4.67 (dd, J=15.3, 6.3 Hz, 1H), 4.39 (dd, J=15.3, 5.4 Hz, 1H),4.02 (dd, J=15.0, 9.0 Hz, 1H), 3.84 (d, J=15.0 Hz, 1H).

EXAMPLES 72˜72 (31)

[2567] By the same procedure as described in Example 28 using carboxylicacids corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and aminederivatives corresponding to (pyridin-3-ylmethyl)amine, and ifnecessary, by converting into the corresponding salts by known methods,the following compounds of the present invention were obtained.

EXAMPLE 724-(1,1-Dimethyl-2-hydroxyethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2568]

[2569] TLC: Rf 0.64 (ethyl acetate);

[2570] NMR (DMSO-d₆): δ 8.05 (brs, 1H), 7.91 (d, J=7.4 Hz, 1H), 7.76 (d,J=7.0 Hz, 1H), 7.75 (d, J=7.4 Hz, 1H), 7.63 (t, J=7.4 Hz, 1H), 7.43 (d,J=7.0 Hz, 1H), 4.87 (t, J=5.8 Hz, 1H), 3.54 (d, J=5.8 Hz, 2H), 1.29 (s,6H).

EXAMPLE 72 (1) 4-(2-Hydroxyethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2571]

[2572] TLC: Rf 0.30 (ethyl acetate);

[2573] NMR (DMSO-d₆): δ 8.72 (t, J=5.6 Hz, 1H), 7.95 (d, J=7.4 Hz, 1H),7.88-7.80 (m, 2H), 7.66 (t, J=7.4 Hz, 1H), 7.45 (d, J=7.0 Hz, 1H), 4.77(t, J=5.6 Hz, 1H), 3.53 (q, J=5.6 Hz, 2H), 3.33 (q, J=5.6 Hz, 2H).

EXAMPLE 72 (2)4-(4-(2-Hydroxyethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2574]

[2575] TLC: Rf 0.45 (ethyl acetate:methanol=9:1);

[2576] NMR (CDCl₃): δ 7.76 (d, J=7.5 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H),7.47 (dd, J=7.5, 1.2 Hz, 1H), 7.32 (dd, J=7.2, 1.2 Hz, 1H), 6.79 (d,J=7.2 Hz, 1H), 4.26-4.19 (m, 1H), 4.03-3.96 (m,1H), 3.88-3.78 (m, 2H),3.35 (br, 2H), 2.72-2.67 (m, 2H), 2.67-2.60 (m, 2H), 2.50-2.42 (m, 2H).

EXAMPLE 72 (3)4-(N-Methyl-N-methoxycarbamoyl)-1,1-dioxidebenzo[b]thiophene

[2577]

[2578] TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

[2579] NMR (CDCl₃) δ 7.78 (dt, J=7.8, 1.0 Hz, 1H), 7.72 (dd, J=7.8, 1.0Hz, 1H), 7.57 (t, J=7.8 Hz, 1H), 7.41 (dd, J=7.0, 1.0 Hz, 1H), 6.76 (d,J=7.0 Hz, 1H), 3.49 (s, 3H), 3.40 (s, 3H).

EXAMPLE 72 (4)4-(4-(Thiazol-2-ylsulfamoyl)phenyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2580]

[2581] TLC: Rf 0.20 (chloroform:methanol 9:1);

[2582] NMR (CDCl₃+DMSO-d₆): δ 10.71 (s, 1H), 7.98 (d, J=7.5 Hz, 1H),7.90-7.67 (m, 6H), 7.67 (t, J=7.8 Hz, 1H), 6.97 (d, J=7.5 Hz, 1H), 6.94(d, J=5 Hz, 1H), 6.52 (d, J=5 Hz, 1H), 5.30 (broad peak, 1H).

EXAMPLE 72 (5) 4-((1R)-1-t-Butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2583]

[2584] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[2585] NMR (CDCl₃): δ 7.95 (dd, J=7.2, 1.0 Hz, 1H), 7.81 (d, J=7.8 Hz,1H), 7.76 (dd, J=7.8, 1.0 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 6.78 (d,J=7.2 Hz, 1H), 6.55 (d, J=8.4 Hz, 1H), 4.64 (dd, J=8.4, 4.5 Hz, 1H),2.36-2.25 (m, 1H), 1.51 (s, 9H), 1.02 (d, J=6.9 Hz, 3H), 0.98 (d, J=6.9Hz, 3H).

EXAMPLE 72 (6)6-(1-Benzylpiperidin-4-yl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2586]

[2587] TLC: Rf 0.44 (ethyl acetate:methanol 4:1);

[2588] NMR (CDCl₃): δ 7.66 (s, 1H), 7.54 (s, 1H), 7.45 (d, J=7.0 Hz,1H), 7.40-7.20 (m, 5H), 6.73 (d, J=7.0 Hz, 1H), 6.40-6.20 (m, 1H),4.10-3.90 (m, 1H), 3.97 (s, 3H), 3.53 (s, 2H), 3.00-2.80 (m, 2H),2.30-2.10 (m, 2H), 2.10-1.90 (m, 2H), 1.70-1.50 (m, 2H).

EXAMPLE 72 (7)6-(2-Diethylaminoethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2589]

[2590] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=14:4:1);

[2591] NMR (CDCl₃): δ 7.71 (s, 1H), 7.57 (s, 1H), 7.46 (d, J=6.9 Hz,1H), 7.10-7.00 (m,1H), 6.71 (d, J=6.9 Hz, 1H), 3.98 (s, 3H), 3.52 (q,J=5.5 Hz, 2H), 2.53 (t, J=5.5 Hz, 2H), 2.28 (s, 6H).

EXAMPLE 72 (8)6-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2592]

[2593] TLC: Rf 0.49 (ethyl acetate:methanol=4:1);

[2594] NMR (DMSO-d₆): δ 9.36 (t, J=6.0 Hz, 1H), 8.58 (s, 1H), 8.48 (d,J=4.5 Hz, 1H), 7.88 (s, 1H), 7.81 (s, 1H), 7.75 (d, J=7.8Hz, 1H), 7.64(d, J=7.0Hz, 1H), 7.42 (d, J=7.0 Hz, 1H), 7.36 (dd, J=7.8, 4.5 Hz, 1H),4.53 (d, J=6.0 Hz, 2H), 3.99 (s, 3H).

EXAMPLE 72 (9)5-(6-Dimethylaminohexyl)oxycarbonyl-1,1-dioxidebenzo[b]thiophene-hydrochloride

[2595]

[2596] TLC: Rf 0.16 (chloroform:methanol=9:1);

[2597] NMR (CDCl₃): δ 12.60-12.30 (br, 1H), 7.96 (d, J=7.4 Hz, 1H),7.54-7.43 (m, 2H), 6.76 (d, J=7.2 Hz, 1H), 4.35 (t, J=6.6 Hz, 2H), 3.97(s, 3H), 3.06-2.90 (m, 2H), 2.81 (s, 3H), 2.79 (s, 3H), 2.03-1.73 (m, 4H), 1.57-1.35 (m, 4H).

EXAMPLE 72 (11)4-(4-t-Butoxycarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2598]

[2599] TLC: Rf 0.65 (methylene chloride:methanol 10:1);

[2600] NMR (CDCl₃): δ 7.78 (dd, J=7.2, 1.2 Hz, 1H), 7.59 (t, J=7.2 Hz,1H), 7.48 (dd, J=7.2, 1.2 Hz, 1H), 7.32 (d, J=6.9 Hz, 1H), 6.80 (d,J=6.9 Hz, 1H), 3.85-3.70 (m, 2H), 3.65-3.45 (m, 2H), 3.45-3.24 (m, 4H),1.47 (s, 9H).

EXAMPLE 72 (11) 4-(Piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophenehydrochloride

[2601]

[2602] TLC: Rf 0.13 (methylene chloride:methanol=10:1);

[2603] NMR (DMSO-d₆): δ 9.35 (bs, 2H), 7.96 (d, J=6.9 Hz, 1H), 7.80-7.73(m, 2H), 7.60 (d, J=7.2 Hz, 1H), 7.51 (d, J=7.2 Hz, 1H), 4.00-3.80 (m,2H), 3.60-3.40 (m, 2H), 3.30-3.15 (m, 2H), 3.15-3.00 (m, 2H).

EXAMPLE 72 (12)4-(4-(4-Methoxyphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2604]

[2605] TLC: Rf 0.50 (methylene chloride:methanol=10:1);

[2606] NMR (DMSO-d₆): δ 7.97 (t, J=4.2 Hz, 1H), 7.71 (d, J=4.2 Hz, 2H),7.58-7.43 (m, 2H), 7.54 (d, J=4.2 Hz, 2H), 7.01 (d, J=8.4 Hz, 2H),4.65-4.50 (m, 1H), 4.30-4.20 (m, 2H), 3.78 (s, 3H), 3.70-3.00 (m, 8H).

EXAMPLE 72 (13)4-(4-(4-Phenylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2607]

[2608] TLC: Rf 0.33 (ethyl acetate);

[2609] NMR (DMSO-d₆): δ 8.00-7.92 (m, 1H), 7.80-7.64 (m, 8H), 7.60-7.35(m, 5H), 4.65-4.50 (m, 1H), 4.48-4.30 (m, 2H), 3.70-3.00 (m, 8H).

EXAMPLE 72 (14)4-(4-(Naphthalen-1-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2610]

[2611] TLC: Rf 0.70 (ethyl acetate);

[2612] NMR (DMSO-d₆): δ 8.42-7.30 (m, 1H), 8.13-7.77 (m, 4H), 7.76-7.40(m, 7H), 4.93-4.76 (m, 2H), 4.66-4.53 (m, 1H), 3.64-3.00 (m, 8H).

EXAMPLE 72 (15)4-(4-(4-Ethylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2613]

[2614] TLC: Rf 0.40 (ethyl acetate);

[2615] NMR (DMSO-d₆): δ 7.98 (t, J=4.2 Hz, 1H), 7.71 (d, J=4.2 Hz, 2H),7.56 (d, J=7.2 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 7.47 (d, J=7.8 Hz, 2H),7.31 (d, J=7.8 Hz, 2H), 4.66-4.45 (m, 1H), 4.33-4.20 (m, 2H), 3.66-3.00(m, 8H), 2.63 (q, J=7.5 Hz, 2H), 1.19 (t, J=7.5 Hz, 3H).

EXAMPLE 72 (16)4-(4-(Naphthalen-2-ylcarbonylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophenehydrochloride

[2616]

[2617] TLC: Rf 0.40 (ethyl acetate);

[2618] NMR (DMSO-d₆): δ 8.72 (s, 1H), 8.20-7.93 (m, 5H), 7.80-7.64 (m,4H), 7.60 (d, J=7.2 Hz, 1H), 7.55 (d, J=7.2 Hz, 1H), 5.30-5.10 (m, 2H),4.60-4.40 (m, 1H), 3.80-3.10 (m, 8H).

EXAMPLE 72 (17)

[2619]4-(4-(Pyridin-2-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[2620] TLC: Rf 0.46 (methylene chloride:methanol=10:1);

[2621] NMR (DMSO-d₆): δ 8.69 (d, J=5.1 Hz, 1H), 8.00-7.90 (m, 2H),7.75-7.64 (m, 3H), 7.60-7.46 (m, 3H), 4.50 (s, 2H), 4.09-3.90 (m,2H),3.67-3.59 (m, 2H), 3.48-3.35 (m, 2H), 3.33-3.20 (m, 2H).

EXAMPLE 72 (18)4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[2622]

[2623] TLC: Rf 0.46 (methylene chloride:methanol=10:1);

[2624] NMR (DMSO-d₆): δ 8.90 (s, 1H), 8.80-8.73 (m, 1H), 8.36-8.30 (m,1H), 7.98-7.92 (m, 1H), 7.80-7.66 (m, 3H), 7.57 (d, J=7.2 Hz, 1H), 7.52(d, J=7.2 Hz, 1H), 4.50-3.00 (m, 10H).

EXAMPLE 72 (19)4-(4-benzoylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2625]

[2626] TLC: Rf 0.52 (methylene chloride:methanol=10:1);

[2627] NMR (CDCl₃): δ 7.79 (d, J=7.5 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H),7.53-7.36 (m, 6H), 7.34 (d, J=6.0 Hz, 1H), 6.81 (d, J=7.5 Hz, 1H),4.00-3.25 (m, 8H).

EXAMPLE 72 (20)4-(4-(Furan-2-ylcarbonyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2628]

[2629] TLC: Rf 0.46 (methylene chloride:methanol=10:1);

[2630] NMR (CDCl₃): δ 7.80 (d, J=6.9 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H),7.51 (d, J=7.8 Hz, 2H), 7.35 (d, J=6.9 Hz, 1H), 7.11 (d, J=3.6 Hz, 1H),6.81 (d, J=6.9 Hz, 1H), 6.52 (d, J=3.6 Hz, 1H), 4.06-3.36 (m, 8H).

EXAMPLE 72 (21)4-(4-Benzylcarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2631]

[2632] TLC: Rf 0.47 (methylene chloride:methanol=10:1);

[2633] NMR (CDCl₃): δ 7.77 (d, J=7.5 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H),7.48-7.14 (m, 6H), 7.28 (d, J=7.2 Hz, 1H), 6.78 (d, J=7.2 Hz, 1H),3.86-3.00 (m, 10H).

EXAMPLE 72 (22)4-(2-(pyrrolidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2634]

[2635] TLC: Rf 0.26 (ethyl acetate:acetic acid:water=3:1:1);

[2636] NMR (CDCl₃): δ 8.00 (dd, J=7.5 Hz and 1 Hz, 1H), 7.79 (dt, J=7.5Hz and 1 Hz, 1H), 7.72 (dd, J=7.5 Hz and 1 Hz, 1H), 7.57 (t, J=7.5 Hz,1H), 6.90 (broad s, 1H), 6.76 (d, J=7.5 Hz, 1H), 3.55 (m, 2H ), 2.73 (t,J=6 Hz, 2H), 2.57 (m, 4H), 1.80 (m, 4H).

EXAMPLE 72 (23)4-(3-(Pyrrolidin-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2637]

[2638] TLC: Rf 0.19 (ethyl acetate acetic acid:water 3:1:1);

[2639] NMR (CDCl₃): δ 9.30 (broad s, 1H), 8.17 (d, J=7.5 Hz, 1H), 7.78(d, J=7.5 Hz, 1H), 7.64 (d, J=7.5 Hz, 1H), 7.52 (t, J=7.5 Hz, 1H), 6.76(d, J=7.5 Hz, 1H), 3.58 (m, 2H), 2.76 (t, J=6 Hz, 2H), 2.5 9 (m, 4H),2.00-1.70 (m, 6H).

EXAMPLE 72 (24)4-(4-(2-Methylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2640]

[2641] TLC: Rf 0.64 (ethyl acetate:hexane=2:1);

[2642] NMR (DMSO-d₆): δ 7.97-7.90 (m, 1H), 7.74-7.65 (m, 2H), 7.57 (d,J=7.2 Hz, 1H), 7.51 (d, J=7.2 Hz, 1H), 7.20-7.10 (m, 2H), 7.06-6.93 (m,2H), 3.90-3.78 (m, 2H), 3.45-3.34 (m, 2H), 3.00-2.90 (m, 2H), 2.85-2.74(m, 2H), 2.27 (s, 3H).

EXAMPLE 72 (25)4-(4-(3-Methylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2643]

[2644] TLC: Rf 0.48 (ethyl acetate:hexane=2:1);

[2645] NMR (DMSO-d₆): δ 8.00-7.92 (m, 1H), 7.74-7.66 (m, 2H), 7.56 (d,J=7.2 Hz, 1H), 7.49 (d, J=7.2 Hz, 1H), 7.14 (t, J=7.8 Hz, 1H), 6.90-6.80(m, 2H), 6.71 (d, J=7.8 Hz, 1H), 3.90-3.80(m, 2H), 3. 46-3.36 (m, 2H),3.36-3.24 (m, 2H), 3.18-3.08 (m, 2H), 2.56 (s, 3H).

EXAMPLE 72 (26)4-(4-(2-Fluorophenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2646]

[2647] TLC: Rf 0.59 (ethyl acetate:hexane=2:1);

[2648] NMR (DMSO-d₆): δ 8.00-7.90 (m, 1H), 7.74-7.66 (m, 2H), 7.56 (d,J=7.2 Hz, 1H), 7.50 (d, J=7.2 Hz, 1H), 7.20-6.96 (m, 4H), 3.90-3.80 (m,2H), 3.46-3.36 (m, 2H), 3.18-3.06 (m, 2H), 3.02-2.90 (m, 2H).

EXAMPLE 72 (27)4-(4-(4-Fluorophenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2649]

[2650] TLC: Rf 0.40 (ethyl acetate:hexane=2:1);

[2651] NMR (DMSO-d₆): δ 8.00-7.90 (m, 1H), 7.74-7.65 (m, 2H), 7.54 (d,J=6.9 Hz, 1H), 7.49 (d, J=6.9 Hz, 1H), 7.14-6.97 (m, 4H), 3.89-3.78 (m,2H), 3.45-3.34 (m, 2H), 3.30-3.19 (m, 2H), 3.13-3.00 (m, 2H).

EXAMPLE 72 (28)4-(4-(4-Methoxyphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2652]

[2653] TLC: Rf 0.22 (ethyl acetate:hexane=2:1);

[2654] NMR (DMSO-d₆): δ 8.00-7.92 (m, 1H), 7.77-7.66 (m, 2H), 7.58 (d,J=6.9 Hz, 1H), 7.50 (d, J=6.9 Hz, 1H), 7.13-7.08 (m, 2H), 6.96-6.86 (m,2H), 4.10-3.70 (m, 2H), 3.72 (s, 3H), 3.54-3.40 (m, 2H), 3.38-3.22 (m,2H), 3.20-3.06 (m, 2H).

EXAMPLE 72 (29)4-(4-(3-Trifluoromethylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2655]

[2656] TLC: Rf 0.47 (ethyl acetate:hexane=2:1);

[2657] NMR (DMSO-d₆): δ 7.98-7.93 (m, 1H), 7.74-7.67 (m, 2H), 7.56 (d,J=6.9 Hz, 1H), 7.49 (d, J=6.9 Hz, 1H), 7.48-7.40 (m, 1H), 7.27-7.16 (m,2H), 7.14-7.07 (m, 1H), 3.88-3.67 (m, 2H), 3.46-3.34 (m, 4H), 3.27-3.18(m, 2H).

EXAMPLE 72 (30)4-((3R)-1-Benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2658]

[2659] TLC: Rf 0.45 (chloroform:methanol=9:1);

[2660] NMR (CDCl₃): δ 7.92 (dd, J=1.0 Hz and 7.0 Hz, 1H), 7.77 (d, J=7.5Hz, 1H), 7.68 (dd, J=1.0 Hz and 7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H),7.40-7.20 (m, 5H), 6.75 (d, J=7.0 Hz, 1H), 6.70 (m, 1H), 4.65 (m, 1H),3.66 (s, 2H), 3.05-2.95 (m, 1H), 2.78 (dd, J=1.0 Hz and 10 Hz, 1H), 2.60(dd, J=6.0 Hz and 10 Hz, 1H), 2.50-2.20 (m, 2H), 1.85-1.70 (m, 1H).

EXAMPLE 72 (31)4-((3S)-1-Benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2661]

[2662] TLC: Rf 0.45 (chloroform:methanol=9:1);

[2663] NMR (CDCl₃): δ 7.92 (dd, J=1.0 Hz and 7.0 Hz, 1H), 7.77 (d, J=7.5Hz, 1H), 7.68 (dd, J=1.0 Hz and 7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H),7.40-7.20 (m, 5H), 6.75 (d, J=7.0 Hz, 1H), 6.70 (m, 1H), 4.65 (m, 1H),3.66 (s, 2H), 3.05-2.95 (m, 1H), 2.78 (dd, J=1.0 Hz and 10 Hz, 1H), 2.60(dd, J=6.0 Hz and 10 Hz, 1H), 2.50-2.20 (m, 2H), 1.85-1.70 (m, 1H).

EXAMPLES 73˜73 (29)

[2664] By the same procedure as described in Example 18 using an alcoholderivative corresponding to the compound prepared in Example 9 (12) anda halogenated compound corresponding to 4-nitrobenzylbromide, or by thesame procedure as described in Example 29 using an alcohol derivativecorresponding to 4-hydroxy-1,1-dioxidebenzo[b]thiophene and an alcoholderivative corresponding to 1-(3-hydroxypropyl)pyrrole, the followingcompounds of the present invention were obtained, with the proviso thatwhen the compounds of the following Examples 73 (26)˜73 (29) wereprepared by the same procedure as described in Example 18, an aqueoussolution of sodium hydroxide was used instead of potassium carbonate.

EXAMPLE 73 5-Acetylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2665]

[2666] TLC: Rf 0.25 (ethyl acetate:hexane:methylene chloride=1:1:1);

[2667] NMR (CDCl₃): δ 7.65 (d, J=8.2Hz, 1H), 7.15 (d, J=6.8Hz, 1H),6.92(dd, J=8.2Hz, 2.2 Hz, 1H), 6.87 (d, J=2.2 Hz, 1H), 6.75 (d, J=6.8 Hz,1H), 4.64 (s, 2H), 2.30 (s, 3H).

EXAMPLE 73 (1) 5-Cyanomethyloxy-1,1-dioxidebenzo[b]thiophene

[2668]

[2669] TLC: Rf 0.36 (hexane:ethyl acetate=1:1);

[2670] NMR (CDCl₃): δ 7.72 (d, J=8.4 Hz, 1H), 7.18 (d, J=7.2 Hz, 1H),7.07 (dd, J=8.4, 2.4 Hz, 1H), 6.98 (d, J=2.4 Hz, 1H), 6.79 (d, J=7.2 Hz,1H), 4.86 (s, 2H).

EXAMPLE 73 (2) 5-t-Butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2671]

[2672] TLC: Rf 0.54 (hexane:ethyl acetate=1:1);

[2673] NMR (CDCl₃): δ 7.63, (d, J=8.4 Hz, 1H), 7.13 (d, J=6.9 Hz, 1H),6.91 (dd, J=8.4, 2.4 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H), 6.73 (d, J=6.9 Hz,1H), 4.58 (s, 2H), 1.49 (s, 9H).

EXAMPLE 73 (3)5-(3-(Ethoxycarbonyl)propyloxy-1,1-dioxidebenzo[b]thiophene

[2674]

[2675] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[2676] NMR (CDCl₃): δ 7.61 (d, J=8.7 Hz, 1H), 7.12 (d, J=6.9 Hz, 1H),6.94 (dd, J=8.7, 2. 0 Hz, 1H), 6.84 (d, J=2.0 Hz, 1H), 6.71 (d, J=6.9Hz, 1H), 4.15 (q, J=7.2 Hz, 2H), 4.08 (t, J=6.6 Hz, 1H), 2.51 (t, J=6.6Hz, 1H), 2.13 (quint, J=6.6 Hz, 1H), 1.26 (t, J 7.2 Hz, 3H).

EXAMPLE 73 (4)5-(4-(Ethoxycarbonyl)butyl)oxy-1,1-dioxidebenzo[b]thiophene

[2677]

[2678] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[2679] NMR (CDCl₃): δ 7.61 (dd, J=8.4, 0.9 Hz, 1H), 7.12 (dd, J=6.9, 0.9Hz, 1H), 6.93 (dd, J=8.4,2.4Hz, 1H), 6.84 (d, J=2.4Hz, 1H), 6.71 (d,J=6.9Hz, 1H), 4.13 (q, J=7.0Hz, 2H), 4.03 (t, J=6.0 Hz, 2H), 2.39 (t,J=7.0 Hz, 2H), 1.88-1.80 (m, 4H), 1.26 (t, J=7.0 Hz, 3H).

EXAMPLE 73 (5) 4-(Pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2680]

[2681] TLC: Rf 0.42 (ethyl acetate:methanol=9:1);

[2682] NMR (CDCl₃): δ 5.19 (s, 2H), 6.63 (d, J=7.0 Hz, 1H), 7.13 (d,J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.37 (dd, J=8.0 Hz, 5.0 Hz, 1H),7.45 (dd, J=7.0 Hz, 1.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.75 (dt, J=8.0Hz, 2.0 Hz, 1H), 8.64 (dd, J=5.0 Hz, 2.0 Hz, 1H), 8.70 (d, J=2.0 Hz,1H).

EXAMPLE 73 (6) 4-(Pyridin-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2683]

[2684] TLC: Rf 0.16 (methylene chloride:ethyl acetate=1:1);

[2685] NMR (CDCl₃): δ 8.66 (d, J=6.0 Hz, 2H), 7.51 (dd, J=7.0, 1.0 Hz,1H), 7.47 (t, J=8.0 Hz, 1H), 7.36-7.31 (m, 3H), 7.03 (d, J=8.0 Hz, 1H),6.67 (d, J=7.0 Hz, 1H), 5.21 (s, 2H).

EXAMPLE 73 (7)4-(4-Trifluoromethylphenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2686]

[2687] TLC: Rf 0.67 (hexane:ethyl acetate=1:2);

[2688] NMR (CDCl₃): δ 7.70 (d, J=7.5 Hz, 2H), 7.60-7.30 (m, 5H), 7.10(d, J=10 Hz, 1H), 6.65 (d, J=7.5 Hz, 1H), 5.25 (s, 2H).

EXAMPLE 73 (8) 4-(3,5-Dimethylisoxazol-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2689]

[2690] TLC: Rf 0.53 (hexane:ethyl acetate=1:2);

[2691] NMR (CDCl₃): δ 7.60-7.40 (m, 1H), 7.40-7.30 (m, 2H), 7.10 (d,J=7.5 Hz, 1H), 6.60 (d, J=7.5 Hz,1H), 4.90 (s, 2H), 2.40 (s, 3H), 2.30(s, 3H).

EXAMPLE 73 (9) 4-(4-Methoxycarbonylphenylmethyl)oxy-1,-dioxidebenzo[b]thiophene

[2692]

[2693] TLC: Rf 0.58 (hexane:ethyl acetate=1:2);

[2694] NMR (CDCl₃): δ 8.10 (d, J=7.5 Hz, 2H), 7.55-7.30 (m, 5H), 7.10(d, J=10 Hz, 1H), 6.65 (d, J=7.5 Hz,1H), 5.25 (s, 2H), 3.95 (s, 3H).

EXAMPLE 73 (10)4-(Benzotriazol-1-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2695]

[2696] TLC: Rf 0.62 (hexane:ethyl acetate 1:2);

[2697] NMR (CDCl₃): δ 8.20-8.10 (m, 1H), 7.70-7.30 (m, 7H), 6.65 (s,2H), 6.60 (d, J=7.5 Hz, 1H).

EXAMPLE 73 (11)4-(2,6-Dimethylphenyl)carbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2698]

[2699] TLC: Rf 0.50 (hexane:ethyl acetate=1:2);

[2700] NMR (CDCl₃): δ 7.65-7.40 (m, 4H), 7.20-7.00 (m, 4H), 6.75 (d,J=7.5 Hz, 1H), 4.80 (s, 2H), 2.20 (s, 6H).

EXAMPLE 73 (12) 4-Trimethylsilylmethyloxy-1,1-dioxi debenzo[b]thiophene

[2701]

[2702] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[2703] NMR (CDCl₃): δ 7.50-7.35 (m, 2H), 7.30-7.10 (m, 2H), 6.60 (d,J=7.5 Hz, 1H), 3.70 (s, 2H), 0.20 (s, 9H).

EXAMPLE 73 (13) 4-(Pyridin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2704]

[2705] TLC: Rf 0.31 (hexane:ethyl acetate=1:2);

[2706] NMR (CDCl₃): δ 8.70-8.55 (m, 1H), 7.85-7.70 (m, 1H), 7.60-7.20(m, 5H), 7.10 (d, J=7.5 Hz, 1H), 6.65 (d, J=7.5 Hz, 1H), 5.35 (s, 2H).

EXAMPLE 73 (14) 4-(2-(Pyridin-3-ylcarbonyl)aminoethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2707]

[2708] TLC: Rf 0.33 (ethyl acetate:methanol=9:1);

[2709] NMR (CDCl₃): δ 8.98 (dd, J=1.8, 0.9 Hz, 1H), 8.72 (dd, J=4.5, 1.8Hz, 1H), 8.12 (d, J=8.0, 1.8 Hz, 1H), 7.49-7.42 (m, 2H), 7.28 (d, J=7.0Hz, 1H), 7.08 (d, J=8.0 Hz, 1H), 6.83 (br, 1H), 6.58 (d, J=7.0 Hz, 1H),4.30 (t, J=5.4 Hz, 2H), 3.93 (q, J=5.4 Hz, 2H).

EXAMPLE 73 (15)4-(3-(Pyridin-3-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene

[2710]

[2711] TLC: Rf 0.32 (ethyl acetate:methanol 10:1);

[2712] NMR (CDCl₃+CD₃OD): δ 8.52-8.25 (m, 2H), 7.80-7.18 (m, 5H), 7.07(d, J=8 Hz, 1H), 6.68 (d, J=7 Hz, 1H), 4.14 (t, J=7 Hz, 2H), 2.87 (t,J=7 Hz, 2H), 2.35-2.10 (m, 2H).

EXAMPLE 73 (16)4-(2-(Pyridin-2-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2713]

[2714] TLC: Rf 0.39 (ethyl acetate:methanol=10:1);

[2715] NMR (CDCl₃): δ 8.57 (d, J=5 Hz, 1H), 7.64 (dt, J=2, 7 Hz, 1H),7.45 (t, J=8 Hz, 1H), 7.35-6.98 (m, 5H), 6.56 (d, J=7 Hz. 1H), 4.50 (t,J=7 Hz, 2H), 3.29 (t, J=7 Hz, 2H).

EXAMPLE 73 (17)4-(1-t-Butoxycarbonylpiperidin-4-yl)oxy-1,1-dioxidebenzo[b]thiophene

[2716]

[2717] TLC: Rf 0.63 (ethyl acetate hexane=1:1);

[2718] NMR (CDCl₃): δ 7.55-7.38 (m, 2H), 7.30 (d, J=8 Hz, 1H), 7.07 (d,J=8 Hz, 1H), 6.23 (d, J=7 Hz, 1H), 4.70-4.50 (m, 1H), 3.85-3.58 (m, 2H),3.50-3.28 (m, 2H), 2.15-1.88 (m, 2H), 1.88-1.66 (m, 2H), 1.47 (s, 9H).

EXAMPLE 73 (18) 4-(5-Methyl-1-tritylimidazol-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2719]

[2720] TLC: Rf 0.11 (hexane:ethyl acetate=1:1);

[2721] NMR (CDCl₃): δ 7.55-7.23 (m, 14H), 7.23-7.00 (m, 6H), 6.56 (d,J=7 Hz, 1H), 5.13 (s, 2H), 1.45 (s, 3H).

EXAMPLE 73(19)4-(1,2,4-oxadiazol-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2722]

[2723] TLC: Rf 0.45 (hexane:ethyl acetate=1:2);

[2724] NMR (DMSO-d₆): δ 9.70 (s, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.57 (d,J=6.9 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.31 (d,J=6.9 Hz, 1H), 5.58 (s, 2H).

EXAMPLE 73 (20) 6-(Pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2725]

[2726] TLC: Rf 0.40 (ethyl acetate);

[2727] NMR (CDCl₃): δ 8.69 (d, J=1.7 Hz, 1H), 8.62 (dd, J=5.0, 1.7 Hz,1H), 7.77 (d, J=7.8 Hz, 1i H), 7.39-7.27 (m, 3H), 7.18 (d, J=7.0 Hz,1H), 7.09 (dd, J=8.2, 2.2 Hz, 1H), 6.58 (d, J=7.0 Hz, 1H), 5.14 (s, 2H).

EXAMPLE 73 (21) 6-(3-Nitrophenylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2728]

[2729] MS (APCI, Pos.): m/z 318 (M+H)⁺.

EXAMPLE 73 (22)6-(3-(t-Butoxycarbonylamino)propyl)oxy-1,1-dioxidebenzo[b]thiophene

[2730]

[2731] TLC: Rf 0.14 (hexane:ethyl acetate=2:1);

[2732] NMR (CDCl₃): δ 7.27-7.23 (m, 2H), 7.16 (d, J=6.9 Hz, 1H), 7.01(dd, J=8.3,-2.3 Hz, 1H), 6.60 (d, J=6.9 Hz, 1H), 4.69 (br, 1H), 4.08 (t,J=6.6 Hz, 2H), 3.32 (q, J=6.6 Hz, 2H), 2.01 (quint, J=6.6 Hz, 2H), 1.44(s, 9H).

EXAMPLE 73 (23) 7-t-Butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2733]

[2734] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[2735] NMR (CDCl₃): δ 7.45 (dd, J=8.5, 7.5 Hz, 1H), 7.12 (d, J=6.9 Hz,1H), 6.94 (d, J=7.5 Hz, 1H), 6.86 (d, J=8.5 Hz, 1H), 6.66 (d, J=6.9 Hz,1H); 4.72 (s, 2H), 1.46 (s, 9H).

EXAMPLE 73 (24)6-(Pyridin-3-yloxy)methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2736]

[2737] TLC: Rf 0.36 (ethyl acetate);

[2738] NMR (CD₃OD): δ 8.35 (d, J=3.0 Hz, 1H), 8.17 (d, J=4.0 Hz, 1H),7.60-7.50 (m, 1H), 7.53 (d, J=7.2 Hz, 1H), 7.45-7.35 (m, 3H), 6.87 (d,J=7.2 Hz, 1H), 5.27 (s, 2H), 3.98 (s, 3H).

EXAMPLE 73 (25) 4,7-Bis(3-hydroxypropyl)-1,1-dioxidebenzo[b]thiophene

[2739]

[2740] TLC: Rf 0.44 (ethyl acetate:methanol=9:1);

[2741] NMR (CDCl₃): δ 7.34 (d, J=7.0 Hz, 1H), 7.04 (d, J=9.2 Hz,1H),6.97 (d, J=9.2 Hz, 1H), 6.54 (d, J=7.0 Hz, 1H), 4.24 (t, J=5.8 Hz, 2H),4.14 (t, J=5.8 Hz, 2H), 3.89 (t, J=5.8 Hz, 2H), 3.83 (t, J=5.8 Hz, 2H),2.00-2.08 (m, 4H).

EXAMPLE 73 (26) 5-Carboxy-4-ethoxy-1,1-dioxidebenzo[b]thiophene

[2742]

[2743] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2744] NMR (CD₃OD): δ 8.00 (d, J=7 Hz, 1H), 7.61 (dd, J=1, 7 Hz, 1H),7.52 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.16 (q, J=7 Hz, 2H),1.42 (t, J=7 Hz, 3H).

EXAMPLE 73 (27) 5-Carboxy-4-butoxy-1,1-dioxidebenzo[b]thiophene

[2745]

[2746] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2747] NMR (CD₃OD): δ 7.98 (d, J=7 Hz, 1H), 7.58 (dd, J=1, 7 Hz,1H),7.51 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.01 (t, J=7 Hz, 2H),1.95-1.66 (m, 2H), 1.66-1.36 (m, 2H), 0.99 (t, J=7 Hz, 3H).

EXAMPLE 73 (28) 5-Carboxy-4-hexyioxy-1,1-dioxidebenzo[b]thiophene

[2748]

[2749] TLC: Rf 0.50 (chloroform:methanol=10:1);

[2750] NMR (CD₃OD): δ 7.98 (d, J=7 Hz, 1H), 7.58 (dd, J=1, 7 Hz, 1H),7.51 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.10 (t, J=7 Hz, 2H),1.95-1.65 (m, 2H), 1.65-1.05 (m, 6H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 73 (29) 5-Carboxy-4-octyloxy-1-dioxidebenzo[b]thiophene

[2751]

[2752] TLC: Rf 0.50 (chloroform:methanol=10:1);

[2753] NMR (CD₃OD): δ 7.98 (d, J=7 Hz, 1H), 7.57 (dd, J=1, 7 Hz, 1H),7.51 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.10 (t, J=7 Hz, 2H),1.95-1.65 (m, 2H), 1.65-1.05 (m, 10H), 0.90 (t, J=7 Hz, 3H).

EXAMPLES 74˜74 (5)

[2754] By the same procedure as described in Example 32 using carboxylicacid derivative corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiopheneand a halogenated compound corresponding to bromoethane, the compoundsof the present invention having the following physical data wereobtained, with the proviso that in the preparation of the compound ofExample 74, 1 mol equivalent of bromoethane was used.

EXAMPLE 74 5-Ethoxycarbonyl-4-hydroxy-1,1-dioxidebenzo[b]thiophene

[2755]

[2756] TLC: Rf 0.32 (hexane:ethyl acetate=2:1);

[2757] NMR (CDCl₃): δπ11.37 (s, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.52 (dd,J=7.0, 0.8 Hz, 1H), 7.24 (dd, J=8.0, 0.8 Hz, 1H), 6.66 (d, J=7.0 Hz,1H), 4.47 (q, J=7.0 Hz, 2H), 1.45 (t, J=7.0 Hz, 3H).

EXAMPLE 74 (1) 5-Ethoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2758]

[2759] TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

[2760] NMR (CDCl₃): δ 7.98 (d, J=7.4 Hz, 1H), 7.49 (t, J=7.4 Hz, 2H),6.75 (d, J=7.4 Hz, 1H), 4.43 (q, J=7.0 Hz, 2H), 3.97 (s, 3H), 1.43 (t,J=7.0 Hz, 3H).

EXAMPLE 74 (2)5-lsopropyloxycarbonyl-4-methoxy-1,1-dinxidebenzo[b]thiophene

[2761]

[2762] TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

[2763] NMR (CDCl₃): δ 7.94 (d, J=7.8 Hz, 1H), 7.52-7.42 (m, 2H), 6.74(d, J=7.2 Hz, 1H), 5.38-5.19 (m, 1H), 3.96 (s, 3H), 1.40 (d, J=6.2 Hz,6H).

EXAMPLE 74 (3)5-(2-Methylpropyl)oxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2764]

[2765] TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

[2766] NMR (CDCl₃): δ 7.97 (d, J=7.8 Hz, 1H), 7.53-7.43 (m, 2H), 6.75(d, J=7.2 Hz, 1H), 4.15 (d, J=6.8 Hz, 2H), 3.97 (s, 3H), 2.20-1.98 (m,1H), 1.03 (d, J=6.6 Hz, 6H).

EXAMPLE 74(4) 6-Methoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2767]

[2768] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[2769] NMR (CDCl₃): δ 7.95 (t, J=1.0 Hz, 1H), 7.75 (d, J=1.0 Hz, 1H),7.46 (dd, J=7.0, 1.0 Hz, 1H), 6.74 (d, J=7.0 Hz, 1H), 3.98 (s, 3H), 3.96(s, 3H).

EXAMPLE 74 (5)6-Methoxymethoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2770]

[2771] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[2772] NMR (CDCl₃): δ 7.99 (s, 1H), 7.79 (s, 1H), 7.47 (d, J=7.0 Hz,1H), 6.76 (d, J=7.0 Hz, 1H), 5.52 (s, 2H), 4.00 (s, 3H), 3.58 (s, 3H).

EXAMPLES 75˜75(2)

[2773] By the same procedure as described in Example 31 using4-bromomethyl-1,1-dioxidebenzo[b]thiophene and amine derivativecorresponding to 2,4-dimethoxybenzylamine hydrochloride, the followingcompounds of the present invention were obtained.

[2774] With the proviso that in the preparation of the compounds ofExample 75 and Example 75 (2), more than 2 mol equivalent of4-bromomethyl-1,1-dioxidebenzo[b]thiophene versus amine derivative.

EXAMPLE 754-(N-(Pyridin-2-ylmethyl)-N-(1,1-dioxidebenzo[b]thiophen-4-ylmethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene

[2775]

[2776] TLC: Rf 0.48 (methanol:methylene chloride=1:10);

[2777] NMR (CDCl₃): δ 8.59 (d, J=4.6 Hz, 1H), 7.72-7.55 (m, 3H),7.55-7.38 (m, 4H), 7.35-7.16 (m, 3H), 7.10 (d, J=7.8 Hz, 1H), 6.68 (d,J=7.0 Hz, 2H), 3.76 (s, 4H), 3.73 (s, 2H).

EXAMPLE 75 (1)4-(Pyridin-2-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[2778]

[2779] TLC: Rf 0.31 (methylene chloride:methanol=10:1);

[2780] NMR (CD₃OD+CDCl₃): δ 8.75-8.52 (m, 1H), 7.96-7.72 (m, 4H), 7.64(t, J=8 Hz, 1H), 7.55-7.25 (m, 2H), 6.93 (d, J=7 Hz, 1H), 4.43 (s, 2H),4.38 (s, 2H).

EXAMPLE 75 (2)4-(N-(2,4-Dimethoxyphenylmethyl)-N-(1,1-dioxidebenzo[b]thiophene-4-ylmethyl)amino) methyl-1,1-dioxidebenzo[b]thiophene

[2781]

[2782] TLC: Rf 0.57 (ethyl acetate:benzene=1:1);

[2783] NMR (CDCl₃): δ 7.65-7.55 (m, 2H), 7.50-7.38 (m, 4H), 7.07-6.99(m, 1H), 6.87 (d, J=7.0 Hz, 2H), 6.57 (d, J=7.0 Hz, 2H), 6.48-6.40 (m,2H), 3.81 (s, 3H), 3.63 (s, 3H), 3.60 (s, 4H), 3.45 (s, 2H).

EXAMPLES 76˜76 (1)

[2784] By the same procedure as described in Example 1 using aderivative corresponding to 1,1-dioxidebenzo[b]thiophene and thiophenol,the following compounds of the present invention were obtained.

EXAMPLE 764,7-Dimethoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2785]

[2786] TLC: Rf 0.27 (hexane:methylene chloride 1:10);

[2787] NMR (CDCl₃): δ 7.52-7.47 (m, 2H), 7.35-7.32 (m, 3H), 7.02 (d,J=8.9 Hz, 1H), 6.91 (d, J=8.9 Hz,1H), 5.00 (dd, J=7.0,1.6 Hz, 1H), 3.92(s, 3H), 3.85 (s, 3H), 3.73 (dd, J=13.9, 7.0 Hz, 1H), 3.59 (dd,J=13.9,1.6 Hz, 1H).

EXAMPLE 76 (1)6-Bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2788]

[2789] TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

[2790] NMR (CDCl₃): δ 7.83 (d, J=1.8 Hz, 1H), 7.75 (dd, J=8.3, 1.8 Hz,1H), 7.58 (d, J=8.3 Hz, 1H), 7.43-7.40 (m, 2H), 7.37-7.34 (m, 3H), 4.88(t, J=6.9 Hz, 1H), 3.80 (dd, J=13.8, 6.9 Hz, 1H), 3.50 (dd, J=13.8, 6.9Hz, 1H).

EXAMPLE 77 5-Acetyloxy-4-nitro-1,1-dioxidebenzo[b]thiophene

[2791]

[2792] By the same procedure as described in Example 12 using5-hydroxy-4-nitro-1,1-dioxidebenzo[b]thiophene instead of the compoundprepared in Example 11, the compound of the present invention having thefollowing physical data was obtained.

[2793] TLC: Rf 0.49 (hexane:ethyl acetate=1:1);

[2794] NMR (DMSO-d₆): δ 8.32 (dd, J=8.0,1.0 Hz,1H),7.78 (d, J=7.0 Hz,1H), 7.76 (d, J=8.0 Hz, 1H), 7.69 (dd, J=7.0, 1.0 Hz, 1H), 2.35 (s, 3H).

EXAMPLES 78˜78 (1)

[2795] By the same procedure as described in Example 7 using thecompounds prepared in Example 35 (39) and Example 35 (47) instead of thecompound prepared in example 6 (8), the following compounds of thepresent invention were obtained.

EXAMPLE 784-(Piperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2796]

[2797] TLC: Rf 0.41 and 0.50 (ethyl acetate:acetic acid:water=3:1:1);

[2798] NMR (CD₃OD): δ 7.85-7.42 (m, 6H), 7.35-7.18 (m 2H), 5.68-5.50 (m,1H), 4.15-3.90 (m, 3H), 3.90-3.50 (m, 2H), 3.50-3.30 (m, 1H), 3.20-2.90(m, 2H), 2.45-2.15 (m, 1H), 2.15-1.40 (m, 4H).

EXAMPLE 78 (1)5-(2-Aminoethyl)oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2799]

[2800] TLC: Rf 0.17 (ethyl acetate:methanol=2:1);

[2801] NMR (DMSO-d₆): δ 8.25 (br, 3H), 8.16 (d, J=8.7 Hz, 1H), 7.86-7.65(m, 6H), 5.99 (d, J=7.2 Hz, 1H), 4.63-4.50 (m, 2H), 4.15-4.00 (m, 2H),3.30-3.26 (m, 2H).

EXAMPLE 794-(2-(2-Hydroxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2802]

[2803] To a solution of the compound prepared in Example 35 (42) (258mg) in ethanol, was added 47% aqueous solution of hydrobromic acid (1.0ml). The mixture was refluxed for 1 hour. The reaction mixture wasconcentrated. The residue was dissolved in ethyl acetate. The mixturewas washed by a saturated aqueous solution of sodium bicarbonate and asaturated aqueous solution of sodium chloride successively, dried overanhydrous sodium sulfate and concentrated. The residue wasrecrystallized from ethyl acetate to give the compound of the presentinvention (174 mg) having the following physical data.

[2804] TLC: Rf 0.22 (ethyl acetate);

[2805] NMR (CDCl₃): δ 7.85-7.72 (m, 2H), 7.66-7.34 (m, 4H), 7.25 (d, J=8Hz, 1H), 6.99 (d, J=8 Hz, 1H), 5.34 (d, J=9 Hz, 1H), 4.19 (d, J=15 Hz,1H), 4.25-3.95 (m, 3H), 3.95-3.55 (m, 7H), 2.50 (brs, 1H).

EXAMPLE 80 4-(4,5-Dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[2806]

[2807] The compound prepared in Example 72 (1) (369 mg) was dissolved indiisopropylethylamine (0.55 ml) and methylene chloride (40 ml). Themixture was cooled to −78° C. Thereto was addedtrifluoromethanesulfonate anhydride (0.30 ml). The mixture was stirredat O° C. for 2.5 hours and thereto was added trifluoromethanesulfonateanhydride (0.15 ml). The mixture was stirred at room temperature for 1hour. To the reaction mixture, were added ethyl acetate and 1Nhydrochloric acid. The mixture was extracted by ethyl acetate. Theextract was washed by 1N sodium hydroxide and a saturated aqueoussolution of sodium chloride successively, dried over anhydrous sodiumsulfate and concentrated. The residue was purified with columnchromatography on silica gel (ethyl acetate:hexane=1:1) to give thecompound of the present invention (97 mg) having the following physicaldata.

[2808] TLC: Rf 0.53 (ethyl acetate);

[2809] NMR (CDCl₃): δ 8.42 (d, J=7.0 Hz, 1H), 8.10 (d, J=7.8 Hz, 1H),7.80 (d, J=7.8 Hz, 1H), 7.57 (t, J=7.8 Hz, 1H), 6.77 (d, J=7.0 Hz, 1H),4.46 (t, J=9.4 Hz, 2H), 4.13 (t, J=9.4 Hz, 2H).

EXAMPLE 80 (1) 5-(4,5-Dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[2810]

[2811] By the same procedure as described in Example 80 using thecompound prepared in Example 28 (25) instead of the compound prepared inExample 72 (1), the compound of the present invention having thefollowing physical data was obtained.

[2812] TLC: Rf 0.39 (ethyl acetate);

[2813] NMR (CDCl₃): δ 8.10 (dd, J=7.8 Hz, 1.2 Hz, 1H), 7.97 (d, J=1.2Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.25 (d, J=6.8 Hz, 1H), 6.78 (d, J=6.8Hz, 1H), 4.50 (t, J=9.6 Hz, 2H), 4.11 (t, J=9.6 Hz, 2H).

EXAMPLES 81˜81 (1)

[2814] By the same procedure as described in Example 52 using thecompounds prepared in Example 45 (10) and Example 35 (63) instead of thecompound prepared in example 51, the following compounds of the presentinvention were obtained.

EXAMPLE 815-Carboxy-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2815]

[2816] TLC: Rf 0.22 (ethyl acetate:methanol=2:1);

[2817] NMR (DMSO-d₆): δ 7.91 (d, J=8.0 Hz, 1H), 7.86-7.74 (m, 3H),7.68-7.61 (m, 2H), 7.56 (d, J=8.0 Hz, 1H), 5.68 (d, J=8.5 Hz, 1H), 4.19(d, J=15.5 Hz, 1H), 4.01 (dd, J=15.5, 8.5 Hz, 1H), 3.66 (s, 3H). 3.35(br, 1H).

EXAMPLE 81 (1)

[2818]4-Carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2819] Free Compound:

[2820] TLC: Rf 0.11 (chloroform:methanol 9:1);

[2821] NMR (DMSO-d₆): δ 13.78 (s, 1H), 8.24 (d, J=7.5 Hz, 1H), 8.05 (d,J=7.8 Hz, 1H), 7.91-7.84 (m, 1H), 7.82-7.74 (m, 3H), 7.69-7.61 (m, 2H),6.27 (dd, J=7.8, 2.1 Hz, 1H), 4.20-3.95 (m, 2H).

[2822] Sodium Salt:

[2823] TLC: Rf 0.11 (chloroform:methanol=9:1);

[2824] NMR (DMSO-d₆): δ 8.22 (dd, J=7.4 Hz and 1.4 Hz, 1H), 7.95-7.85(m, 3H), 7.85-7.70 (m, 2H), 7.70-7.55 (m, 2H), 6.62 (dd, J=8.0 Hz and2.0 Hz, 1H), 4.10 (dd, J=15 Hz and 8.0 Hz, 1H), 3.95 (dd, J=15 Hz and2.0 Hz, 1H).

EXAMPLE 824-Formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2825]

[2826] To a solution of the compound prepared in Example 45 (20) (1.46g) in methylene chloride (40 ml), were added pyridinium dichromate (2.44g) and magnesium sulfate (1.0 g). The mixture was stirred at roomtemperature for 6 hours. The undissolved ingredients were filtered off.The filtrate was poured onto 1N hydrochloric acid. The mixture wasextracted by ethyl acetate. The extract was washed by a saturatedaqueous solution of sodium chloride, dried over magnesium sulfate andconcentrated. The residue was washed by methanol to give the compound ofthe present invention (1.03 g) having the following physical data.

[2827] TLC: Rf 0.65 (chloroform:methanol=9:1);

[2828] NMR (DMSO-d₆): δ 10.29 (s, 1H), 8.29 (dd, J=7.4, 1.2 Hz, 1H),8.16 (dd, J=7.6,1.2 Hz, 1H), 8.03-7.92 (m, 1H), 7.86-7.72 (m, 3H),7.71-7.57 (m, 2H), 6.41 (dd, J=8.0, 2.2 Hz, 1H), 4.08 (dd, J=15.2, 8.0Hz, 1H), 3.97 (dd, J=15.2, 2.2 Hz, 1H).

EXAMPLES 83˜83 (3)

[2829] By the same procedure as described in Example 21 using thecompounds prepared in Example 73 (2), Example 73 (23), Example 28 (12)and Example 72 (5) instead of the compound prepared in Example 20 (27),the following compounds of the present invention were obtained.

EXAMPLE 83 5-Carboxymethyloxy-1,1-dioxidebenzo[b]thiophene

[2830]

[2831] TLC: Rf 0.18 (ethyl acetate:methanol=5:1);

[2832] NMR (DMSO-d₆): δ 7.75 (dd, J=8.3, 0.9 Hz, 1H), 7.53 (dd, J=6.9,0.9 Hz, 1H), 7.34 (d, J=6.9 Hz, 1H), 7.16 (d, J=2.7 Hz, 1H), 7.07 (dd,J=8.3, 2.7 Hz, 1H), 4.83 (s, 2H).

EXAMPLE 83 (1) 7-Carboxymethyloxy-1,1-dioxidebenzo[b]thiophene

[2833]

[2834] TLC: Rf 0.21 (ethyl acetate:methanol=4:1);

[2835] NMR (DMSO-d₆): δ 7.57 (t, J=7.8 Hz, 1H), 7.51 (d, J=6.9 Hz, 1H),7.25 (d, J=6.9 Hz, 1H), 7.11 (d, J=7.8 Hz, 2H), 4.92 (s, 2H).

EXAMPLE 83 (2)4-((1S)-1-Carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2836]

[2837] TLC: Rf 0.16 (ethyl acetate:methanol=4:1);

[2838] NMR (DMSO-d₆): δ 8.89 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.3 Hz, 1H),7.81 (d, J=7.3 Hz, 1H), 7.77 (d, J=7.3 Hz, 1H), 7.69 (t, J=7.3 Hz, 1H),7.48 (d, J=7.3 Hz, 1H), 4.33 (dd, J=7.8, 6.0 Hz, 1H), 2.23-2.12 (m, 1H),0.97 (d, J=6.6 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H).

EXAMPLE 83 (3)4-((1R)-1-Carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2839]

[2840] TLC: Rf 0.16 (ethyl acetate:methanol=4:1);

[2841] NMR (DMSO-d₆): δ 8.89 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.3 Hz, 1H),7.81 (d, J=7.3 Hz, 1H), 7.77 (d, J=7.3 Hz, 1H), 7.69 (t, J=7.3 Hz, 1H),7.47 (d, J=7.3 Hz, 1H), 4.33 (dd, J=7.8, 6.0 Hz, 1H), 2.25-2.13 (m, 1H),0.97 (d, J=6.6 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H).

EXAMPLE 84 5-(3-Carboxypropyl) oxy-1,1-dioxidebenzo[b]thiophene

[2842]

[2843] To a solution of the compound prepared in Example 73 (3) (98 mg)in dimethylsulfoxide (5.0 ml) were added phosphate buffer (pH 7.4, 25ml) and porcine liver esterase (100 μl). The mixture was stirred at roomtemperature for 18 hours. The reaction mixture was poured onto 1 Nhydrochloric acid. The mixture was extracted by ethyl acetate. Theextract was washed by a saturated aqueous solution of sodium chloride,dried over anhydrous magnesium sulfate and concentrated to give thecompound of the present invention (90 mg) having the following physicaldata.

[2844] TLC: Rf 0.26 (chloroform:methanol=9:1);

[2845] NMR (CDCl₃): δ 7.62 (d, J=8.4 Hz, 1H), 7.13 (d, J=6.8 Hz, 1H),6.95 (dd, J=8.4, 2.2 Hz, 1H), 6.85 (d, J=2.2 Hz, 1H), 6.73 (d, J=6.8 Hz,1H), 4.10 (t, J=6.2 Hz, 2H), 2.58 (t, J=7.0 Hz, 2H), 2.24-2.07 (m, 2H).

EXAMPLE 84 (1) 5-((2E)-3-Carboxy-2-propenyl)oxy-1,1-dioxidebenzo[b]thiophene

[2846]

[2847] By the same procedure as described in Example 84 using thecompound prepared in Example 30 (13) instead of the compound prepared inExample 73 (3), the compound of the present invention having thefollowing physical data was obtained.

[2848] TLC: Rf 0.14 (chloroform:methanol=9:1);

[2849] NMR (CD₃OD): δ 7.64 (d, J=8.8 Hz, 1H), 7.38 (d, J=7.0 Hz, 1H),7.16-7.00 (m, 3H), 6.95 (d, J=7.0 Hz, 1H), 6.13 (dt, J=15.8, 2.0 Hz,1H), 4.89-4.80 (m, 2H).

EXAMPLE 855-(4-Phenylbutyl)aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2850]

[2851] To a solution of 4-Phenylbutylamine (164 mg) and the compoundprepared in example 15 (366 mg) in methylene chloride (3.0 ml), wasadded sodium sulfate (1.0 g) at room temperature. The mixture wasstirred for 1 hour. To the reaction mixture were added sodiumborocyanohydride (63 mg), methanol (3.0 ml) and 4N solution of hydrogenchloride in dioxane (0.3 ml). The mixture was stirred at roomtemperature for 1 hour. The reaction mixture was concentrated. To theresidue was added chloroform. The undissolved ingredients were filteredoff. The filtrate was concentrated. The residue was purified with columnchromatography on silica gel (chloroform:methanol=100:5) to give thecompound of the present invention (340 mg) having the following physicaldata, and then converted into hydrochloride by a known method to givethe compound of the present invention having the following physicaldata.

[2852] Free Compound:

[2853] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2854] NMR (CDCl₃): δ 7.80-7.50 (m, 6H), 7.33-7.12 (m, 6H), 5.34 (d,J=4.8 Hz, 1H), 4.15-3.90 (m, 4H), 3.75 (s, 3H), 2.98 (t, J=7.8 Hz, 2H),2.63 (t, J=7.8 Hz, 2H), 1.88-1.60 (m, 4H).

[2855] Hydrochloride:

[2856] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2857] NMR (CDCl₃): δ 9.49 (bs, 2H), 7.93 (d, J=8.1 Hz, 1H), 7.77-7.70(m, 2H), 7.65 (t, J=8.1 Hz, 1H), 7.50 (t, J=8.1 Hz, 2H), 7.35-7.12 (m,6H), 5.27 (d, J=8.1 Hz, 1H), 4.18-4.02 (m, 2H), 3.98 (d, J=15.0 Hz, 1H),3.88 (s, 3H), 3.85 (dd, J=15.0, 8.1 Hz, 1H), 3.00-2.85 (m, 2H), 2.63 (t,J=7.5 Hz, 2H), 2.00-1.60 (m, 4H).

EXAMPLE 85 (1)5-(Pyridin-3-ylmethyl)aminomethyl-4-methoxy-3-phenysulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2858]

[2859] By the same procedure as described in Example 85 using thecompound prepared in Example 15, and (pyridin-3-ylmethyl)amine insteadof 4-phenylbutylamine, the compound of the present invention having thefollowing physical data was obtained. And then, by converting intohydrochloride using the obtained compound by a known method, thecompound of the present invention having the following physical data wasobtained.

[2860] Free Compound:

[2861] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2862] NMR (CDCl₃): δ 8.59 (d, J=2.0 Hz, 1H), 8.55 (dd, J=4.8, 2.0 Hz,1H), 7.80-7.65 (m, 4H), 7.58 (d, J=6.0 Hz, 1H), 7.43 (dd, J=7.6, 2.0 Hz,3H), 7.30 (dd, J=7.6, 4.8 Hz, 1H), 5.20 (d, J=8 .2 Hz, 1H), 4.17 (d,J=13.4 Hz, 1H), 3.95-3.70 (m, 5H), 3.80 (s, 3H).

[2863] 2hydrochloride:

[2864] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2865] NMR (DMSO-d₆): δ 10.35 (brs, 1H), 10.15 (bs, 1H), 9.03 (s, 1H),8.85 (d, J=5.2 Hz, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.06 (d, J=8.4 Hz, 1H),7.95-7.72 (m, 4H), 7.70-7.55 (m, 3H), 5.85-5.77 (m, 1H), 4.40-4.00 (m,6H), 3.69 (s, 3H).

EXAMPLE 866-Dimethylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2866]

[2867] By the same procedure as described in Example 8 using thecompound prepared in Example 35 (68) instead of the compound prepared inExample 7, the compound of the present invention having the followingphysical data was obtained.

[2868] TLC: Rf 0.48 (hexane:ethyl acetate=1:2);

[2869] NMR (DMSO-d₆): δ 7.81-7.74 (m, 3H), 7.66-7.58 (m, 2H), 7.40 (d,J=9.0 Hz, 1H), 7.09 (dd, J=9.0, 2.5 Hz, 1H), 6.80 (d, J=2.5 Hz, 1H),5.56 (dd, J=9.5, 3.0 Hz,1H), 3.91 (dd, J=15.0, 9.5 Hz, 1H), 3.67 (dd,J=15.0, 3.0 Hz, 1H), 2.99 (s, 6H).

EXAMPLE 874-(2-Dimethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2870]

[2871] By the same procedure as described in Example 28 using thecompound prepared in Example 81 (1) instead of4-carboxy-1,1-dioxidebenzo[b]thiophene, and (2-dimethylaminoethyl)amineinstead of (pyridin-3-ylmethyl)amine, and then by converting intohydrochloride by known methods, the following compound of the presentinvention was obtained.

[2872] TLC: Rf 0.62 (chloroform:methanol:triethylamine=8:2:1);

[2873] NMR (DMSO-d₆): δ 10.40-10.20 (br, 1H), 9.19 (t, J=5.4Hz, 1H),8.13 (d, J=6.9 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.87 (d, J=7.8 Hz, 1H),7.84-7.72 (m, 3H), 7.67-7.58 (m, 2H), 6.27 (d, J=9.0 Hz, 1H), 4.13 (dd,J=9.0,15.0 Hz, 1H), 3.96 (d, J=15.0 Hz, 1H), 3.77-3.55 (m, 2H),3.40-3.22 (m, 2H), 2.87-2.74 (m, 6H).

EXAMPLES 88˜88 (2)

[2874] Using the compounds prepared in Example 18 (40), Example 20 (4)and Example 45 (3) instead of the compound prepared in Example 1 by thesame procedure as described in Example 3 or by the same reaction using3-chloroperbenzoic acid instead of OXONE@ as an oxidizer, the followingcompounds of the present invention were prepared.

EXAMPLE 884,7-Bis(pyridin-3-ylmethyloxy)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2875]

[2876] TLC: Rf 0.36 (ethyl acetate:methanol=2:1);

[2877] NMR (CDCl₃): δ 8.65-8.60 (m, 3H), 8.57 (dd, J=5.0,1.5 Hz, 1H),7.90-7.80 (m, 2H), 7.68-7.65 (m, 2H), 7.60-7.55 (m, 1H), 7.41-7.31 (m,4H), 7.01 (d, J=9.0 Hz,1H), 6.98 (d, J=9.0 Hz, 1H), 5.25 (d, J=13.0 Hz,1H), 5.21 (dd, J=9.5, 1.0 Hz, 1H), 5.20 (d, J=13.0 Hz,1H), 4.96 (d,J=12.0 Hz, 1H), 4.87 (d, J=12.0 Hz, 1H), 4.12 (dd, J=15.0, 1.0 Hz, 1H),3.75 (dd, J=15.0, 9.5 Hz, 1H).

EXAMPLE 88 (1)4-(N-Oxidepyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2878]

[2879] TLC: Rf 0.30 (ethyl acetate:methanol=2:1);

[2880] NMR (DMSO-d₆): δ 8.29 (s, 1H), 8.20 (d, J=6.2 Hz, 1H), 7.73-7.57(m, 4H), 7.51-7.31 (m, 6H), 5.77 (d, J=8.8 Hz, 1H), 5.10 (d, J=12.8 Hz,1H), 4.90 (d, J=12.8 Hz, 1H), 4.18 (d, J=15.0 Hz, 1H), 3.95 (dd, J=15.0,8.8 Hz, 1H).

EXAMPLE 88 (2)4-(2-(N-Oxidepyridin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2881]

[2882] TLC: Rf 0.23 (ethyl acetate:methanol=9:1);

[2883] NMR (DMSO-d₆): δ 8.11 (d, J=6.9 Hz, 2H), 7.79-7.72 (m, 3H),7.65-7.60 (m, 3H), 7.34 (d, J=7.5 Hz, 1H), 7.28-7.25 (m, 3H), 5.41 (d,J=8.5 Hz, 1H), 4.16 (d, J=15.0 Hz, 1H), 4.15-3.90 (m, 2H), 4.02 (dd,J=15.0, 8.5 Hz, 1H), 2.88-2.66 (m, 2H).

EXAMPLE 894-methoxy-3-(4-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2884]

[2885] By the same procedure as describe in 1 using the compoundprepared in example 28 (27) instead of 1,1-dioxidebenzo[b]thiophene and4-mercaptphenol instead of thiophenol, the compound of the presentinvention having the following physical data was obtained.

[2886] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[2887] NMR (CDCl₃): δ 7.60-7.00 (m, 3H), 7.35 (d, J=7.5 Hz, 2H), 6.80(d, J=7.5 Hz, 2H), 6.00 (s, 1H), 4.90 (dd, J=5.0, 1.2 Hz, 1H), 3.90 (s,3H), 3.75-3.50 (m, 2H)

EXAMPLE 90 4-Methoxy-3-(4-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2888]

[2889] By the same procedure as described in Example 18 using thecompound prepared in Example 89 instead of the compound prepared inExample 9 (12) and a halogenated compound corresponding to4-nitrobenzylbromide, the compound of the present invention having thefollowing physical data was obtained.

[2890] TLC: Rf 0.22 (ethyl acetate).

EXAMPLE 914-Methoxy-3-(4-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2891]

[2892] By the same procedure as described in Example 3 using thecompound prepared in Example 90 instead of the compound prepared inExample 1, the compound of the present invention having the followingphysical data was obtained.

[2893] TLC: Rf 0.39 (ethyl acetate:triethylamine=95:5);

[2894] NMR (DMSO-d₆): δ 9.05 (br.s, 1H), 8.90 (d, J=5.0 Hz, 1H), 8.55(d, J=7.5 Hz, 1H), 8.00 (dd, J=7.5, 5.0 Hz, 1H), 7.80-8.60 (m, 3H),7.50-7.15 (m, 4H), 5.60-5.40 (m, 3H), 4.20 (d, J=15 Hz, 1H), 4.00 (dd,J=15, 7.5 Hz, 1H), 3.45 (s, 3H).

Examples 92˜92 (1)

[2895] By the same procedure as described in Example 1 using thecompounds prepared in Example 28 (27) and Example 28 (26) instead of1,1-dioxidebenzo[b]thiophene, and thiophenol, the following compounds ofthe present invention were obtained.

EXAMPLE 925-(2-Dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2896]

[2897] TLC: Rf 0.40 (ethyl acetate:methanol:triethylamine=8:1:1);

[2898] NMR (CDCl₃): δ 8.10 (d, J=8.0 Hz, 1H), 7.67 (br, 1H), 7.55-7.48(m, 3H), 7.39-7.36 (m, 3H), 5.10 (dd, J=6.5, 2.0 Hz, 1H), 4.06 (s, 3H),3.71 (dd, J=14.0, 6.5 Hz, 1H), 3.61 (dd, J=14.0, 2.0 Hz, 1H), 3.57 (q,J=6.0 Hz, 2H), 2.53 (t, J=6.0 Hz, 2H), 2.29 (s, 6H).

EXAMPLE 92 (1)5-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro1,1-dioxidebenzo[b]thiophene

[2899]

[2900] TLC: Rf 0.46 (ethyl acetate:methanol=9:1);

[2901] NMR (CDCl₃): δ 8.60-8.52 (m, 2H), 8.06 (d, J=8.0 Hz, 1H),7.77-7.74 (m, 2H), 7.53-7.45 (m, 3H), 7.37-7.30 (m, 4H), 5.03 (dd,J=6.5, 2.0 Hz, 1H), 4.67 (d, J=6.0 Hz, 2H), 3.92 (s, 3H), 3.70 (dd,J=14.0, 6.5 Hz, 1H), 3.58 (dd, J=14.0, 2.0 Hz, 1H).

EXAMPLE 934-(2-(Piperidin-1-yl)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[2902]

[2903] By the same procedure as described in Example 31 using4-bromomethyl-1,1-dioxidebenzo[b]thiophene, and1-(2-aminoethyl)piperidine instead of 2,4-dimethoxybenzylamine-hydrochloride, the compound of the present invention having thefollowing physical data was obtained. And then, the obtained compoundwas converted into hydrochloride by a known method to give the compoundof the present invention having the following physical data.

[2904] Free Compound:

[2905] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=90:5:5);

[2906] NMR (CDCl₃): δ 7.75-7.60 (m, 2H), 7.60-7.40 (m, 2H), 6.70 (d,J=7.5 Hz, 1H), 3.90 (s, 2H), 2.70 (t, J=7.5 Hz, 2H), 2.50-2.20 (m, 4H),2.40 (t, J=7.5 Hz, 2H), 1.65-1.35 (m, 6H).

[2907] 2hydrochloride:

[2908] TLC: Rf 0.28 (ethyl acetate:methanol:triethylamine=8:1:0.5);

[2909] NMR (DMSO-d₆+pyridine-d₅): δ 8.15 (d, J=7.5 Hz, 1H), 8.00 (d,J=7.5 Hz, 1H), 7.90 (d, J=7.5 Hz, 1H), 7.70 (t, J=7.5 Hz, 1H), 7.50 (d,J=7.5 Hz, 1H), 4.40 (s, 2H), 3.55-3.30 (m, 4H), 3.30-3.10 (m, 4H),1.90-1.70 (m, 4H), 1.65-1.50 (m, 2H).

EXAMPLE 944-(2-(Piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2910]

[2911] By the same procedure as described in Example 27 using thecompound prepared in Example 93 instead of5-methyl-1,1-dioxidebenzo[b]thiophene, the compound of the presentinvention having the following physical data was obtained. And then, theobtained compound was converted into hydrochloride by a known method togive the compound of the present invention having the following physicaldata.

[2912] Free Compound:

[2913] TLC: Rf 0.18 (ethyl acetate:methanol:triethylamine=90:5:5);

[2914] NMR (CDCl₃): δ 7.80-7.40 (m, 8H), 6.10 (d, J=10 Hz, 1H), 4.60 (d,J=15 Hz, 1H), 3.95 (d, J=15 Hz, 1H), 3.90 (d, J=15 Hz, 1H), 3.75 (dd,J=15, 10 Hz, 1H), 2.80-2.60 (m, 2H), 2.60-2.20 (m, 6H), 1.60-1.30 (m,6H).

[2915] 2hydrochloride:

[2916] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1:0.5);

[2917] NMR (DMSO-d₆+pyridine-d₅): δ 8.35 (d, J=7.5 Hz, 1H), 8.00-7.75(m, 5H), 7.65 (t, J=7.5 Hz, 2H), 6.70 (d, J=7.5 Hz, 1H), 4.80 (d, J=15Hz, 1H), 4.50 (d, J=15 Hz, 1H), 4.20-3.95 (m, 2H), 3.65-3.35 (m, 4H),3.30-3.00 (m, 4H), 2.00-1.70 (m, 4H), 1.70-1.40 (m, 2H).

EXAMPLE 95 4-t-Butoxycarbonylaminobenzo[b]thiophene

[2918]

[2919] To a suspension of 4-carboxybenzo[b]thiophene (3.2 g) int-butanol (170 ml), were added triethylamine (7.5 ml) anddiphenylphosphorylamide (4.2 ml). The mixture was stirred at 95° C. for2 hours. The precipitate was filtered off and the filtrate wasconcentrated. The residue was extracted with ethyl acetate. The extractwas washed by water, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified with column chromatopgaphy onsilica gel (hexane:ethyl acetate=5:1) to give the compound of thepresent invention (3.0 g) having the following physical data.

[2920] TLC: Rf 0.41 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.81-7.78(m, 1H), 7.60 (d, J=8.0 Hz, 1H), 7.44-7.24 (m, 3H), 6.74 (br, 1H), 1.55(s, 9H).

EXAMPLE 96 4-t-Butoxycarbonylamino-1,1-dioxidebenzo[b]thiophene

[2921]

[2922] To a solution of the compound prepared in Example 95 (3.0 g) inchloroform (100 ml) was added m-chloroperbenzoic acid (8.2 g) at 0° C.The mixture was stirred at room temperature for 3 hours. The reactionmixture was concentrated. The residue was extracted with ethyl acetate.The extract was washed by an aqueous solution of sodium hydroxide, waterand a saturated solution of sodium chloride successively, dried overanhydrous magnesium sulfate and concentrated. The residue was dissolvedin methylene chloride and was allowed to stand overnight. The crystalsthat appeared were filtered. The filtrate was concentrated. The residuewas purified with column chromatography on silica gel (methylenechloride), combined with the said crystals, to give the compound of thepresent invention (3.0 g) having the following physical data.

[2923] TLC: Rf 0.41 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.83-7.80(m, 1H), 7.49 (t, J=7.5 Hz, 1H), 7.46-7.43 (m, 1H), 7.31 (dd, J=7.2, 1.0Hz,1H), 6.70 (d, J=7.2 Hz,1H), 6.54 (br,1H), 1.53 (s, 9H).

EXAMPLE 97 4-Amino-1,1-dioxidebenzo[b]thiophene hydrochloride

[2924]

[2925] To a solution of the compound prepared in Example 96 (2.5 g) inethyl acetate (30 ml) was added 4N solution of hydrogen chloride inethyl acetate (10 ml). The mixture was stirred at room temperature for 3hours. After removing the solvent, the residue was washed by ethylacetate to give the compound of the present invention (1.8 g) having thefollowing physical data.

[2926] TLC: Rf 0.29 (hexane:ethyl acetate=1:2);

[2927] NMR (CD₃OD): δ 7.63 (dd, J=7.0, 1.0 Hz, 1H), 7.61 (t, J=7.5 Hz,1H), 7.54 (dt, J=7.5,1.0 Hz, 1H), 7.42 (dd, J=7.5, 1.0 Hz, 1H), 7.08 (d,J=7.0 Hz, 1H).

EXAMPLE 98 4-(4-Fluorobenzylcarbonylamino)-1,1-dioxidebenzo[b]thiophene

[2928]

[2929] To a solution of the compound prepared in Example 97 (100 mg),4-fluorophenylacetic acid (192 mg) and triethylamine (1 ml) indimethylformamide (3 ml) was added propanephosphonic acid cyclicanhydride (50 % solution in dimethylformamide; 3 ml). The mixture wasstirred at room temperature for 1.5 hours. To the reaction mixture wasadded ethyl acetate. The mixture was washed by water, a saturatedaqueous solution of sodium bicarbonate and a saturated aqueous solutionof sodium chloride, and concentrated. The residue was purified withcolumn chromatography on silica gel (hexane:ethyl acetate=1:1), followedby recrystallization from ethyl acetate-hexane to give the compound ofthe present invention having the following physical data.

[2930] TLC: Rf 0.63 (ethyl acetate);

[2931] NMR (DMSO-d₆): δ 10.27 (s, 1H), 7.88-7.82 (m, -1H), 7.64 (d,J=7.0 Hz, 1H), 7.61-7.55 (m, 2H), 7.41-7.34 (m, 3H), 7.16 (t, J=9.0 Hz,2H), 3.75 (s, 2H).

EXAMPLES 98 (1)˜98 (5)

[2932] By the same procedure as described in Example 98 using thecompound prepared in Example 97 and a carboxylic acid derivativecorresponding to 4-fluorophenylacetic acid, the compounds of the presentinvention having the following physical data.

EXAMPLE 98 (1) 4-(Pyridin-3-ylcarbonyl)amino-1,1-dioxidebenz[b]thiophene

[2933]

[2934] TLC: Rf 0.18 (ethyl acetate);

[2935] NMR (DMSO-d₆): δ 10.69 (s, 1H), 9.17 (d, J=2.0 Hz, 1H), 8.80 (dd,J=5.0, 2.0 Hz,1H), 8.34 (dt, J=7.8, 2.0 Hz, 1H), 7.82 (dd, J=7.5, 1.5Hz, 1H), 7.72-7.63 (m, 3H), 7.60 (dd, J=7.8, 5.0 Hz, 1H), 7.36 (d, J=7.2Hz, 1H).

EXAMPLE 98 (2) 4-(3-Chlorobenzoyl) amino-1,1-dioxidebenzo[b]thiophene

[2936]

[2937] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[2938] NMR (DMSO-d₆): δ 10.62 (s, 1H), 8.07 (t, J=1.5Hz, 1H), 7.96 (dt,J=7.7,1.5 Hz, 1H), 7.78 (dd, J=7.7, 1.5 Hz, 1H), 7.73-7.64 (m, 4H), 7.60(t, J=7.7 Hz, 1H), 7.35 (d, J=6.6 Hz,1H).

EXAMPLE 98 (3) 4-Benzylcarbonylamino-1,1-dioxidebenzo[b]thiophene

[2939]

[2940] TLC: Rf 0.45 (hexane:ethyl acetate=1:2);

[2941] NMR (CDCl₃): δ 7.75-7.72 (m, 1H), 7.48-7.35 (m, 7H), 7.29 (br,1H), 6.79 (d, J=7.2 Hz, 1H), 6.58 (d, J=7.2 Hz, 1H), 3.79 (s, 2H).

EXAMPLE 98 (4) 4-(Dimethylaminoacetyl)amino-1,1-dioxidebenzo[b]thiophene

[2942]

[2943] TLC: Rf 0.31 (ethyl acetate:methanol=4:1);

[2944] NMR (CDCl₃): δ 9.52 (br, 1H), 8.06 (m, 1H), 7.56-7.48 (m, 2H),7.28-7.25 (m, 1H), 6.73 (d, J=7.0 Hz, 1H), 3.15 (s, 2H), 2.44 (s, 6H).

EXAMPLE 98 (5) 4-Acetylamino-1,1-dioxidebenzo[b]thiophene

[2945]

[2946] TLC: Rf 0.25 (ethyl acetate);

[2947] NMR (DMSO-d₆): δ 1 0.05 (s, 1H), 7.89-7.83 (m, 1H), 7.70 (d,J=7.0 Hz, 1H), 7.61-7.55 (m, 2H), 7.33 (d, J=7.0 Hz, 1H), 2.12 (s, 3H).

EXAMPLES 99˜99 (10)

[2948] By the same procedure as described in Example 28 using4-carboxy-1,1-dioxidebenzo[b]thiophene (prepared in Example 107hereinafter described) and a corresponding amine derivative instead of(pyridin-3-ylmethyl)amine, and if necessary, by converting into thecorresponding salt by known methods by a known method, the compounds ofthe present invention having the following physical data were obtained.

EXAMPLE 994-(3-(2-Oxopyrrolidin-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2949]

[2950] TLC: Rf 0.36 (chloroform:methanol=9:1);

[2951] NMR (CDCl₃): δ 8.19 (dd, J=7.0 Hz and 1.0 Hz, 1H), 8.05 (broad s,1H), 7.95 (dd, J=8.0 Hz and 1.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.60(t, J=8.0 Hz, 1H), 6.75 (d, J=7.0 Hz, 1H), 3.50-3.35 (m, 6H), 2.46 (t,J=8.0 Hz, 2H), 2.20-2.00 (m, 2H), 1.90-1.70 (m, 2H).

EXAMPLE 99 (1)4-(2-Dimethylaminoethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2952]

[2953] TLC: Rf 0.20 (ethyl acetate:acetic acid:water=3:1:1);

[2954] NMR (CDCl₃): δ 8.03 (dd, J=7.2 Hz and 1.0 Hz, 1H), 7.79 (dt,J=7.8 Hz and 1.0 Hz, 1H), 7.69 (dd, J=7.8 Hz and 1.0 Hz, 1H), 7.57 (t,J=7.8 Hz, 1H), 6.77 (d, J=7.2 Hz, 1H), 3.49 (m, 2H), 2.67 (t, J=6.0 Hz,2H), 2.58 (q, J=7.2 Hz, 4H), 1.04 (t, J=7.2 Hz, 6H).

EXAMPLE 99 (2)4-(2-(N-Ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2955]

[2956] TLC: Rf 0.61 (chloroform:methanol 9:1);

[2957] NMR (CDCl₃): δ 7.91 (d, J=7.0 Hz, 1H), 7.74 (m, 1H), 7.55-7.40(m, 2H), 7.13 (dd, J=9.0 Hz and 7.4 Hz, 1H), 6.73 (d, J=7.0 Hz, 1H),6.70-6.55 (m, 3H), 6.35 (broad s, 1H), 3.75-3.50 (m, 4H), 3.19 (q, J=7.0Hz, 2H), 2.29 (s, 3H), 1.16 (t, J=7.0 Hz, 3H).

EXAMPLE 99 (3) 4-(2,4,6-Trimethoxybenzyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2958]

[2959] TLC: Rf 0.63 (chloroform:methanol=9:1);

[2960] NMR (CDCl₃+DMSO-d₆): δ 7.89 (d, J=7.0 Hz, 1H), 7.80-7.65 (m, 3H),7.55 (t, J=7.4 Hz, 1H), 6.88 (d, J=7.0 Hz, 1H), 6.17 (s, 2H), 4.56 (d,J=4.8 Hz, 2H), 3.84 (s, 6H), 3.82 (s, 3H).

EXAMPLE 99 (4)4-(4-(2-Hydroxyethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thioiphene.hydrochloride

[2961]

[2962] TLC: Rf 0.33 (methylene chloride:methanol=10:1);

[2963] NMR (DMSO-d₆): δ 8.00-7.93 (m, 1H), 7.76-7.66 (m, 2H), 7.58 (d,J=6.9 Hz, 1H), 7.52 (d, J=6.9 Hz, 1H), 5.40 (bs, 1H), 4.64-4.46 (m, 1H),6.85-3.73 (m, 2H), 3.70-3.00 (m, 10H).

EXAMPLE 99 (5) 4-(4-Benzyloxycarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2964]

[2965] TLC: Rf 0.64 (methylene chloride:methanol=10:1);

[2966] NMR (CDCl₃): δ 7.78 (d, J=7.5 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H),7.47 (d, J=7.5 Hz, 1H), 7.36 (s, 5H), 7.32 (d, J=6.9 Hz, 1H), 6.79 (d,J=6.9 Hz, 1H), 5.16 (s, 2H), 3.88-3.72 (m, 2H), 3.70-3.56 (m, 2H),3.54-3.40 (m, 2H), 3.40-3.25 (m, 2H).

EXAMPLE 99 (6) 4-(N-Ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2967]

[2968] TLC: Rf 0.25 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.80-7.20(m, 4H), 6.75 (d, J=6.8 Hz, 1H), 3.80-3.50 (m, 2H), 3.35-3.10 (m, 2H),2.70-2.10 (m, 6H), 1.70-1.20 (m, 6H), 1.26 and 1.06 (each t, J=7.0 Hz,total 3H).

EXAMPLE 99 (7)4-(3-(Imidazol-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2969]

[2970] TLC: Rf 0.43 (chloroform:methanol=4:1);

[2971] NMR (CDCl₃): δ 7.95 (d, J=7.0 Hz, 1H), 7.72 (d, J=7.6 Hz, 1H),7.69 (d, J=7.6 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.55 (broad s, 1H), 7.41(s, 1H), 6.98 (s, 1H), 6.96 (s, 1H), 6.76 (d, J=7.0 Hz, 1H), 4.07 (t,J=6.6 Hz, 2H), 3.44 (q, J=6.6 Hz, 2H), 2.14 (m, 2H).

EXAMPLE 99 (8)4-(N-2-(Piperidin-1-yl)ethyl-N-methyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2972]

[2973] TLC: Rf 0.30 (methylene chloride:methanol=9:1);

[2974] NMR (CDCl₃): δ 7.85-7.30 (m, 4H), 6.76 (d, J=7.2 Hz, 1H), 3.74and 3.30 (each t, J=6.0 Hz, total 2H), 3.14 and 2.88 (each s, total 3H),2.70-2.10 (m, 6H), 1.70-1.30 (m, 6H).

EXAMPLE 99 (9)4-(4-(1,3-Dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2975]

[2976] TLC: Rf 0.26 (ethyl acetate);

[2977] NMR (DMSO-d₆): δ 8.00-7.92 (m, 1H), 7.74-7.65 (m, 2H), 7.56 (d,J=6.9 Hz, 1H), 7.52 (d, J=6.9 Hz, 1H), 7.21 (s, 1H), 7.03-6.95 (m, 2H),6.07 (s, 2H), 4.64-4.50 (m, 1H), 4.28-4.15 (m, 2H), 3.70-2.96 (m, 8H).

EXAMPLE 99 (10)4-(4-((2E)-3-Phenyl-2-propenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophenehydrochloride

[2978]

[2979] TLC: Rf 0.10 (ethyl acetate);

[2980] NMR (DMSO-d₆): δ 8.00-7.92 (m, 1H), 7.76-7.65 (m, 2H),7.58 (d,J=6.9 Hz, 1H), 7.53-7.46 (m, 2H),7.51 (d, J=6.9 Hz, 1H), 7.45-7.28 (m,3H), 6.84 (d, J=15.3 Hz, 1H), 6.47-6.33 (m, 1H), 4.60 (m,1H), 3.98-3.84(m, 2H), 3.70-2.97 (m, 8H).

EXAMPLES 100˜100 (24)

[2981] By the same procedure as described in Example 28 using thecompound prepared in Example 81 (1) instead of4-carboxy-1,1-dioxidebenzo[b]thiophene, and an amine derivative insteadof (pyridin-3-yl)ethylamine, and if necessary, by converting into thecorresponding salt by a known method, the following compounds of thepresent invention having the following physical data were obtained.

EXAMPLE 1004-(Furan-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2982]

[2983] TLC: Rf 0.43 (hexane:ethyl acetate=1:2);

[2984] NMR (DMSO-d₆): 8 9.29 (t, J=5.5 Hz, 1H), 7.99 (d, J=7.6 Hz, 1H),7.95 (d, J=7.6 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.79-7.76 (m, 3H),7.67-7.60 (m, 3H), 6.48-6.35 (m, 2H), 6.25 (d, J=9.0 Hz, 1H), 4.55 (dd,J=15.5, 5.5 Hz, 1H), 4.40 (dd, J=15.5, 5.5 Hz, 1H), 4.10 (dd, J=15.3,9.0 Hz, 1H), 4.00 (d, J=15.3 Hz, 1H).

EXAMPLE 100 (1)4-(2,4,6-Trimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2985]

[2986] TLC: Rf 0.55 (ethyl acetate);

[2987] NMR (DMSO-d₆): δ 8.40 (t, J=4.8 Hz, 1H), 7.89-7.86 (m, 2H),7.86-7.69 (m, 4H), 7.67-7.58 (m, 2H), 6.25 (s, 2H), 6.18 (dd, J=8.1, 2.1Hz, 1H), 4.46-4.30 (m, 2H), 4.11-3.94 (m, 2H), 3.77 (s, 9H).

EXAMPLE 100 (2)4-(3-(2-Oxopyrrolidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2988]

[2989] TLC: Rf 0.44 (ethyl acetate:methanol=2:1);

[2990] NMR (CDCl₃): δ 8.20-8.08 (m, 1H), 8.02 (d, J=7.5 Hz, 1H),7.83-7.62 (m, 5H), 7.59-7.49 (m, 2H), 6.40 (dd, J=9.3, 1.2 Hz, 1H),3.89-3.61 (m, 4H), 3.51-3.33 (m, 2H), 3.32-3.20 (m, 1H), 3.20-3.06 (m,1H), 2.53-2.33 (m, 2H), 2.15-1.88 (m, 3H), 1.85-1.74 (m,1H).

EXAMPLE 100 (3)4-((3S)-1-Benzylpyrrolidin-3-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2991]

[2992] More Polar Compound:

[2993] TLC: Rf 0.27 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[2994] NMR (CDCl₃): δ 7.90-7.80 (m, 4H), 7.75-7.66 (m, 2H), 7.62-7.53(m, 2H), 7.37-7.13 (m, 5H), 6.70 (d, J=8.7 Hz, 1H), 6.24-6.17 (m, 1H),4.74-4.62 (m, 1H), 3.80 (dd, J=15.0,1.5 Hz, 1H), 3.68 (d, J=12.9 Hz,1H), 3.63 (dd, J=15.0, 9.3 Hz, 1H), 3.57 (d, J=12.9 Hz, 1H), 3.00-2.86(m, 2H), 2.72 (dd, J=9.9, 6.3 Hz, 1H), 2.51-2.31 (m, 2H), 1.89-1.77 (m,1H).

[2995] Less Polar Compound:

[2996] TLC: Rf 0.35 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[2997] NMR (CDCl₃): δ 7.94-7.87 (m, 2H), 7.87-7.78 (m, 2H), 7.75-7.66(m, 2H), 7.64-7.56 (m, 2H), 7.41-7.23 (m, 5H), 6.73 (d, J=8.1 Hz, 1H),6.28-6.21 (m, 1H), 4.71-4.59 (m, 1H), 3.80 (dd, J=14.7, 1.2 Hz, 1H),3.64 (s, 2H), 3.62 (dd, J=14.7, 9.3 Hz, 1H), 2.95-2.84 (m, 1H),2.80-2.67 (m, 2H), 2.46-2.30 (m, 2H), 2.12-1.95 (m, 1H).

[2998] The determination of the absolute configuration of * is notperformed, but the said more polar and less polar isomers are eachsingle optically active compounds.

EXAMPLE 100 (4)4-(2-(Pyrrolidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2999]

[3000] Free Compound:

[3001] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3002] NMR (CDCl₃): δ 7.93-7.78 (m, 4H), 7.75-7.66 (m, 2H), 7.63-7.53(m, 2H), 7.10 (brs, 1H), 6.31-6.24 (m, 1H), 3.83 (dd, J=15.0, 1.5 Hz,1H), 3.73-3.49 (m, 3H), 2.80 (t, J=5.7 Hz, 2H), 2.69-2.53 (m, 4H),1.86-1.73 (m, 4H).

[3003] Hydrochloride:

[3004] TLC: Rf 0.37 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3005] NMR (DMSO-d₆): δ 9.18 (t, J=5.4 Hz, 1H), 8.14 (d, J=7.5 Hz, 1H),7.96-7.90 (m, 1H), 7.85 (t, J=7.5 Hz, 1H), 7.81-7.72 (m, 3H), 7.67-7.58(m, 2H), 6.27 (d, J=9.3 Hz, 1H), 4.13 (dd, J=15.6, 9.3 Hz, 1H), 3.96 (d,J=15.6 Hz, 1H), 3.78-3.50 (m, 4H), 3.48-3.28 (m, 2H), 3.06-2.94 (m, 2H),2.09-1.78 (m, 4H).

EXAMPLE 100 (5)4-(2-Diethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3006]

[3007] Free Compound:

[3008] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3009] NMR (CDCl₃): δ 7.92-7.80 (m, 4H), 7.76-7.66 (m, 2H), 7.62-7.56(m, 2H), 7.03 (brs, 1H), 6.29 (dd, J=9.0, 1.5 Hz, 1H), 3.84 (dd, J=14.4,1.5 Hz, 1H), 3.72-3.44 (m, 3H), 2.73 (t, J=6.0 Hz, 2H), 2.60 (q, J=7.2Hz, 4H), 1.04 (t, J=7.2 Hz, 6H).

[3010] Hydrochloride:

[3011] TLC: Rf 0.49 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3012] NMR (DMSO-d₆): δ 10.32 (brs, 1H), 9.30-9.20 (m, 1H), 8.08 (d,J=7.5 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.86 (t, J=7.5 Hz, 1H), 7.82-7.72(m, 3H), 7.68-7.58 (m, 2H), 6.29 (d, J=9.3 Hz, 1H), 4.12 (dd, J=15.6,9.3 Hz, 1H), 3.96 (d, J=15.6 Hz, 1H), 3.80-3.57 (m, 2H), 3.40-3.08 (m,6H), 1.24 (t, J=7.2 Hz, 6H).

EXAMPLE 100 (6) 4-(2-(N-Ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3013]

[3014] Free Compound:

[3015] TLC: Rf 0.49 (ethyl acetate:triethylamine=6:0.5);

[3016] NMR (CDCl₃): δ 7.94-7.87 (m, 2H), 7.82 (d, J=6.9 Hz, 1H),7.75-7.67 (m, 1H), 7.67-7.54 (m, 4H), 7.17-7.11 (m, 1H), 6.72-6.64 (m,2H), 6.56 (d, J=7.8 Hz, 1H), 6.49 (brs, 1H), 6.26 (dd, J=9.0, 1.2 Hz,1H), 3.81 (dd, J=14.7, 1.2 Hz, 1H), 3.77-3.47 (m, 5H), 3.43 (q, J=7.2Hz, 2H), 2.30 (s, 3H), 1.15 (t, J=7.2 Hz, 3H).

[3017] Hydrochloride:

[3018] TLC: Rf 0.47 (ethyl acetate:triethylamine=6:0.5);

[3019] NMR (CD₃OD): δ 7.98-7.60 (m, 6H), 7.59-7.26 (m, 6H), 6.36-6.15(m, 1H), 4.09-3.89 (m, 4H), 3.88-3.40 (m, 4H), 2.44 (s, 3H), 1.17 (t,J=7.2 Hz, 3H).

EXAMPLE 100 (7)4-(N-Ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3020]

[3021] Free Compound:

[3022] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3023] NMR (CDCl₃): δ 8.00-7.55 (m, 8H), 5.85 (d, J=8 Hz, 1H), 3.85-3.30(m, 6H), 2.85-2.50 (m, 2H), 2.55 (m, 2H), 2.40 (m, 2H), 1.80-1.40 (m,6H), 1.34 and 1.36 (each t, J=7 Hz, total 3H).

[3024] Hydrochloride:

[3025] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3026] NMR (CDCl₃+DMSO-d₆): δ 11.30 (broad s, 1H), 7.95-7.60 (m, 8H),5.89 (d, J=8 Hz, 1H), 4.20-3.80 (m, 3H), 3.80-3.20 (m, 7H), 3.00 (m,2H), 2.11 (m, 2H), 2.00 (m, 3H), 1.50 (m, 1H), 1.41 (t, J=7 Hz, 3H).

EXAMPLE 100 (8)4-(3-(Imidazol-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3027]

Free Compound:

[3028] TLC: Rf 0.50 (methylene chloride:methanol=4:1);

[3029] NMR (CDCl₃): δ 7.90-7.50 (m, 9H), 7.56 (s, 1H), 6.98 (s, 1H),6.93 (s, 1H), 6.27 (dd, J=2 Hz and 7 Hz, 1H), 4.20-3.95 (m, 2H),3.80-3.55 (m, 3H), 3.30 (m, 1H), 2.13 (m, 2H).

[3030] Hydrochloride:

[3031] TLC: Rf 0.50 (methylene chloride:methanol=4:1);

[3032] NMR (CDCl₃+DMSO-d₆): δ 9.59 (s, 1H), 9.49 (t-like, 1H), 8.23 (t,J=4.4 Hz, 1H), 7.85-7.60 (m, 5H), 7.60-7.40 (m, 4H), 7.29 (s, 1H), 6.23(dd, J=4.0 Hz and 6.8 Hz, 1H), 4.65-4.35 (m, 2H), 3.82 (m, 2H), 3.65 (m,1H), 3.25 (m, 1H), 2.40 (m, 1H), 2.20 (m, 1H).

EXAMPLE 100 (9)4-((3R)-1-Benzylpyrrolidin-3-yl)carbamoyl-3-phenylsuilfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3033]

[3034] Less Polar Compound:

[3035] TLC: Rf 0.35 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[3036] NMR (CDCl₃) δ 7.94-7.87 (m, 2H), 7.87-7.78 (m, 2H), 7.75-7.67 (m,2H), 7.64-7.56 (m, 2H), 7.38-7.26 (m, 5H), 6.68 (d, J=8.1 Hz, 1H),6.28-6.20 (m, 1H), 4.73-4.59 (m, 1H), 3.80 (dd, J=14.7, 1.5 Hz, 1H),3.66 (s, 2H), 3.63 (dd, J=14.7, 9.3 Hz, 1H), 2.96-2.87 (m, 1H),2.82-2.66 (m, 2H), 2.47-2.30 (m, 2H), 2.12-1.86 (m, 1H).

[3037] More Polar Compound:

[3038] TLC: Rf 0.27 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[3039] NMR (CDCl₃): δ 7.90-7.78 (m, 4H), 7.74-7.65 (m, 2H), 7.62-7.52(m, 2H), 7.36-7.13 (m, 5H), 6.79 (d, J=8.4 Hz, 1H), 6.25-6.18 (m, 1H),4.72-4.60 (m, 1H), 3.80 (dd, J=15.0,1.5 Hz, 1H), 3.65 (d, J=12.9 Hz,1H), 3.62 (dd, J=15.0, 9.0 Hz, 1H), 3.54 (d, J=12.9 Hz, 1H), 2.96-2.83(m, 2H), 2.72 (dd, J=9.9, 6.3 Hz, 1H), 2.49-2.32 (m, 2H), 1.90-1.73 (m,1H).

[3040] The determination of the absolute configuration of * is notperformed, but the said more polar and less polar isomers are eachsingle optically active compounds.

EXAMPLE 100 (10)4-(3-(Pyrrolidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3041]

[3042] Free Compound:

[3043] TLC: Rf 0.25 (methanol:ethyl acetate:triethylamine=2:4:0.5);

[3044] NMR (CDCl₃): δ 9.16-9.06 (m, 1H), 7.91-7.84 (m, 2H), 7.84-7.77(m, 2H), 7.75-7.62 (m, 2H), 7.61-7.53 (m, 2H), 6.44-6.37 (m, 1H), 3.85(dd, J=14.7, 1.2 Hz, 1H), 3.80-3.61 (m, 2H), 3.59-3.44 (m, 1H),2.91-2.72 (m, 2H), 2.71-2.59 (m, 4H), 2.00-1.63 (m, 6H).

[3045] Hydrochloride:

[3046] TLC: Rf 0.26 (methanol:ethyl acetate:triethylamine=2:4:0.5);

[3047] NMR (DMSO-d₆): δ 10.43 (brs, 1H), 9.00 (t, J=5.7 Hz, 1H), 8.02(d, J=7.5 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.90-7.74 (m, 4H), 7.71-7.61(m, 2H), 6.30 (d, J=9.0 Hz, 1H), 4.11 (dd, J=15.0, 9.0 Hz, 1H), 3.94 (d,J=15.0 Hz, 1H), 3.60-3.10 (m, 6H), 3.10-2.78 (m, 2H), 2.11-1.73 (m, 6H).

EXAMPLE 100 (11)4-(N-2-(Piperidin-1-yl)ethyl-N-methyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3048]

[3049] Free Compound:

[3050] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3051] NMR (CDCl₃): δ 8.05-7.55 (m, 8H), 5.88 (dd, J=8.8 Hz and 2.0 Hz,1H), 4.00-3.55 and 3.30 (each m, total 4H), 3.20 and 3.17 (each s, total3H), 2.80-2.35 (m, 6H), 1.70-1.40 (m, 6H)

[3052] Hydrochloride:

[3053] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3054] NMR (DMSO-d₆): δ 10.49 (broad s, 1H), 8.15 (d, J=6.2 Hz, 1H),8.00-7.60 (m, 7H), 5.87 (d, J=8.8 Hz, 1H), 4.25-3.70 (m, 4H), 3.70-2.80(m, 6H), 3.33 and 3.16 (each s, total 3H), 2.00-1.60 (m, 5H), 1.44 (m,1H).

EXAMPLE 100 (12) 4-(3,5-Dimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3055]

[3056] TLC: Rf 0.45 (methylene chloride:ethyl acetate=4:1);

[3057] NMR (DMSO-d₆): δ 9.26 (t, J=5.8 Hz, 1H), 7.78 (d, J=7.6 Hz, 1H),7.91 (dd, J=7.6, 1.0 Hz, 1H), 7.84 (dd, J=7.0, 1.0 Hz, 1H), 7.13 (t,J=7.6 Hz, 1H), 7.45 (d, J=7.0 Hz, 1H), 6.51 (d, J=2.2 Hz, 2H), 6.39 (t,J=2.2 Hz, 1H), 4.42 (d, J=5.8 Hz, 2H), 3.73 (s, 6H).

EXAMPLE 100 (13) 4-(3-(Piperidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[3058]

[3059] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3060] NMR (DMSO-d₆): δ 10.40 (broad s, 1H), 9.08 (t, J=5.3 Hz, 1H),8.10-7.60 (m, 8H), 6.33 (d, J=9.2 Hz, 1H), 4.13 (dd, J=15.0 Hz and 9.2Hz, 1H), 3.94 (d, J=15.0 Hz, 1H), 3.60-3.00 (m, 6H), 2.80 (m, 2H),2.05(t, J=6.5 Hz, 2H), 1.73 (m, 5H), 1.36 (m,1H).

EXAMPLE 100 (14)4-(2-Diisopropylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3061]

[3062] TLC: Rf 0.46 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3063] NMR (DMSO-d₆): δ 10.01 (s, 1H), 9.27 (t, J=5.7 Hz, 1H), 8.09 (d,J=7.0 Hz, 1H), 7.97 (d, J=7.0 Hz, 1H), 7.88 (t, J=7.0 Hz, 1H), 7.80-7.76(m, 3H), 7.68-7.60 (m, 2H), 6.36 (d, J=9.0 Hz, 1H), 4.11 (dd, J=15.3 Hzand 9.0 Hz, 1H), 3.96 (d, J=15.3 Hz,1H), 3.90-3.60 (m, 4H), 3.33 (m,1H), 3.18 (m, 1H), 1.42 (d, J=6.6 Hz, 3H), 1.38 (d, J=6.6 Hz, 3H), 1.34(d, J=6.6 Hz, 3H), 1.32 (d, J=6.6 Hz, 3H).

EXAMPLE 100 (15)4-(2-(Morpholin-4-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzolb]thiophene.hydrochloride

[3064]

[3065] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3066] NMR (DMSO-d₆): δ 11.14 (broad s, 1H), 9.27 (broad t-like, 1H),8.13 (d, J=7.5 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.86 (t, J=7.5 Hz, 1H),7.82-7.70 (m, 3H), 7.70-7.60 (m, 2H), 6.30 (d, J=8.4 Hz, 1H), 4.14 (dd,J=15.6 Hz and 8.4 Hz, 1H), 4.00-3.65 (m, 7H), 3.65-3.00 (m, 6H).

EXAMPLE 100 (16)4-(N-2-(Piperidin-1-yl)ethyl-N-propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[3067]

[3068] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3069] NMR (DMSO-d₆): δ 10.70 and 10.66 (each broad s, total 1H),8.00-7.65 (m, 8H), 5.83 (d, J=8.7 Hz, 1H), 4.14 (dd, J=15.3 Hz and 8.7Hz, 1H), 4.00-3.70 (m, 3H), 3.65-3.10 (m, 6H), 3.10-2.80 (m, 2H),2.00-1.60 (m, 6H), 1.40 (m, 1H), 0.98 and 0.86 (each t, J=7.2 Hz, total3H).

EXAMPLE 100 (17)4-(N-2-(Piperidin-1-yl)ethyl-N-isopropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3070]

[3071] TLC;Rf 0.55 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3072] NMR (DMSO-d₆): δ 10.78 (broad s, 1H), 8.00-7.60 (m, 8H), 5.90 (d,J=9.2 Hz, 1H), 4.40-4.03 (m, 3H), 4.00-2.80 (m, 8H), 2.00-1.60 (m, 5H),1.40 (m, 1H), 1.44 and 1.28 and 1.04 (each d, J=6.4 Hz, total 6H).

EXAMPLE 100 (18)4-(4-Benzoylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3073]

[3074] TLC: Rf 0.48 (methylene chloride:methanol=10:1);

[3075] NMR (DMSO-d₆): δ 7.95-7.80 (m, 3H), 7.80-7.56 (m, 5H), 7.42 (s,5H), 5.92 (dd, J=9.0, 1.5 Hz, 1H), 4.40-4.00 (m, 2H), 3.90-3.40 (m, 6H),3.72 (dd, J=15.0, 1.5 Hz, 1H), 3.65 (dd, J=15.0, 9.0 H z, 1H).

EXAMPLE 100 (19)4-(4-(4-Ethylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3076]

[3077] TLC: Rf 0.55 (methylene chloride:methanol 10:1);

[3078] NMR (DMSO-d₆): δ 7.88-7.73 (m, 6H), 7.67-7.63 (m, 2H), 7.47 (d,J=7.0 Hz, 2H), 7.21 (d, J=7.0 Hz, 2H), 5.87 (dd, J=10.0, 1.5 Hz, 1H),4.16 (bs, 2H), 4.05 (dd, J=15.0, 10.0 HZ, 1H), 3.79 (dd, J=15.0, 1.5 Hz,1H), 3.30-2.90 (m, 8H), 2.58 (q, J=8.0 Hz, 2H), 1.17 (t, J=8.0 Hz, 3H).

EXAMPLE 100 (20)4-(4-(4-Phenylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1dioxidebenzo[b]thiophene.hydrochloride

[3079]

[3080] TLC: Rf 0.55 (methylene chloride:methanol=10:1);

[3081] NMR (DMSO-d₆): δ 7.88-7.78 (m, 3H), 7.78-7.72 (m, 3H), 7.67-7.58(m, 7H), 7.48-7.41 (m, 3H), 7.38-7.34 (m, 1H), 5.88 (d, J=9.5 Hz, 1H),4.21 (bs, 2H), 4.10-3.70 (m, 8H), 4.06 (dd, J=15.5, 9.5 Hz, 1H), 3.79(d, 15.5 Hz, 1H), 3.19 (s, 2H).

EXAMPLE 100 (21)4-(4-(1,3-Dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3082]

[3083] TLC: Rf 0.54 (methylene chloride:methanol=10:1);

[3084] NMR (DMSO-d₆): δ 7.86-7.76 (m, 4H), 7.74 (d, J=8.0 Hz, 2H), 7.64(t, J=8.0 Hz, 2H), 7.08 (bs, 1H), 6.98-6.92 (m, 1H), 6.83 (d, J=8.0 Hz,1H), 5.96-5.92 (m, 2H), 5.86 (d, J=8.5 Hz, 1H), 4.15-3.70 (m, 2H), 4.04(dd, J=15.0, 8.5 Hz, 1H), 3.78 (d, J=15.0 Hz, 1H), 3.15-2.80 (m, 8H).

EXAMPLE 100 (22)4-(4-Benzyloxycarbonylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3085]

[3086] TLC: Rf 0.80 (methylene chloride:methanol=10:1);

[3087] NMR (DMSO-d₆): δ 7.96-7.80 (m, 4H), 7.76 (d, J=7.5 Hz, 2H), 7.66(t, J=7.5 Hz, 2H), 7.45-7.36 (m, 5H), 5.89 (d, J=8.7 Hz, 1H), 5.11 (s,2H), 4.13 (dd, J=14.7, 8.7 Hz, 1H), 3.93 (d, J=14.7 Hz, 1H), 3.80-3.40(m, 8H).

EXAMPLE 100 (23)4-(4-(2-Methylphenyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-diozidebenzo[b]thiophenehydrochloride

[3088]

[3089] TLC: Rf 0.80 (methylene chloride:methanol=10:1);

[3090] NMR (DMSO-d₆): δ 7.97-7.90 (m, 2H), 7.90-7.74 (m, 4H), 7.74-7.63(m, 2H), 7.23-7.10 (m, 2H), 7.10-6.83 (m, 2H), 5.92 (d, J=9.6 Hz, 1H),4.15 (dd, J=15.3, 9.6 Hz, 1H), 3.93 (d, J=15.3 Hz, 1H), 3.92-3.80 (m,2H), 3.08-2.90 (m, 6H), 2.30 (s, 3H).

EXAMPLE 100 (24) 4-(4-(4-Methoxyphenyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[3091]

[3092] TLC: Rf 0.75 (methylene chloride:methanol=10:1); NMR (DMSO-d₆): δ8.02-7.92 (m, 2H), 7.92-7.73 (m, 4H), 7.72-7.64 (m, 2H), 7.36-7.14 (m,2H), 7.00-6.90 (m, 2H), 5.91 (d, J=9.6 Hz, 1H), 4.20-3.76 (m, 4H), 4.14(dd, J=15.3, 9.6 Hz, 1H), 3.93 (d, J=15.3 Hz, 1H), 3.72 (s, 3H),3.45-3.26 (m, 4H).

EXAMPLES 101˜101 (1)

[3093] By the same procedure as described in Example 1 using thecompounds prepared in Examples 28 (11) and 73 (16) instead of1,1-dioxidebenzo[b]thiophene, the following compounds of the presentinvention were obtained.

EXAMPLE 1014-2-(Piperidin-1-yl)ethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3094]

[3095] TLC: Rf 0.40 (methanol:water:acetic acid=1:1:0.1);

[3096] NMR (CDCl₃): δ 7.81 (dd, J=7.6, 1.1 Hz, 1H), 7.75 (dd, J=7.6, 1.1Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.56-7.53 (m, 2H), 7.38-7.35 (m, 3H),6.91 (br, 1H), 5.74 (dd, J=7.3, 1.3 Hz, 1H), 3.72 (dd, J=13.9, 7.3 Hz,1H), 3.68-3.58 (m, 1H), 3.60 (dd, J=13.9, 1.3 Hz, 1H), 3.55-3.45 (m,1H), 2.55 (t, J=5.8 Hz, 2H), 2.38 (br, 4H), 1.56-1.48 (m, 4H), 1.44-1.39(m, 2H).

EXAMPLE 101 (1)4-(2-(Pyridin-2-yl)ethyl)oxy-3-phenylthio-1,1-dioxidebenzo[b]thiophene

[3097]

[3098] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[3099] NMR (CDCl₃): δ 8.54 (ddd, J=4.8, 1.7, 1.0 Hz, 1H), 7.54 (dt,J=7.7, 1.7 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.43-7.40 (m, 2H), 7.34-7.22(m, 5H), 7.15-7.10 (m, 2H), 4.91 (dd, J=6.9, 1.8 Hz, 1H), 4.52 (t, J=6.6Hz, 2H), 3.66 (dd, J=13.8, 6.9 Hz, 1H), 3.57 (dd, J=13.8, 1.8 Hz, 1H),3.31 (t, J=6.6 Hz, 2H).

EXAMPLE 1024-(2-(Piperidin-1-yl)ethyl)carbamoyl-3-(4-nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3100]

[3101] By the same procedure as described in Example 27 using thecompound prepared in Example 28 (11) instead of5-methyl-1,1-dioxidebenzo[b]thiophene, and 4-nitrobenzenesulfonic acidsodium salt instead of benzenesulfonic acid sodium salt, and ifnecessary, by converting into hydrochloride by a known method, thecompounds of the present invention having the following physical datawere obtained.

[3102] Free Compound:

[3103] TLC: Rf 0.40(methanol:water:acetic acid=5:5:0.5);

[3104] NMR (CDCl₃): δ 8.35 (d, J=8.7 Hz, 2H), 8.01 (d, J=8.7 Hz, 2H),7.91 (dd, J=7.5,1.7 Hz, 1H), 7.81 (dd, J=7.5, 1.7 Hz, 1H), 7.76 (t,J=7.5 Hz, 1H), 7.59 (br, 1H), 6.42 (dd, J=9.2, 1.5 Hz, 1H), 3.88 (dd,J=15.0,1.5 Hz, 1H), 3.75 (dd, J=15.0, 9.2 Hz, 1H), 3.75-3.64 (m, 1H),3.57-3.48 (m, 1H), 2.77-2.65 (m, 2H), 2.53 (br, 4H), 1.66-1.57 (m, 4H),1.52-1.45 (m, 2H).

[3105] Hydrochloride:

[3106] TLC: Rf 0.40 (methanol:water:acetic acid=5:5:0.5);

[3107] NMR (DMSO-d₆): δ 9.98 (br, 1H), 9.28 (br, 1H), 8.42 (d, J=8.7 Hz,2H), 8.11 (d, J=7.5 Hz, 1H), 8.03 (d, J=8.7 Hz, 2H), 7.97 (d, J=7.5 Hz,1H), 7.89 (t, J=7.5 Hz, 1H), 6.41 (dd, J=7.3, 3.2 Hz, 1H), 4.16 (dd,J=15.5, 7.3 Hz, 1H), 4.10 (dd, J=15.5, 3.2 Hz, 1H), 3.72-3.70 (m, 2H),3.57-3.48 (m, 2H), 3.32-3.25 (m, 2H), 2.96 (br, 2H), 1.82-1.68 (m, 5H),1.45-1.35 (m, 1H).

EXAMPLES 103˜103 (41)

[3108] By the same procedure as described in Example 31 using4-methylsulfonyloxymethyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiopheneinstead of 4-bromomethyl-1,1-dioxidebenzo[b]thiophene and an aminederivative corresponding to 2,4-dimethoxybenzylamine hydrochloride, andif necessary, by converting into the corresponding salt by a knownmethod, the following compounds of the present invention were obtained.

EXAMPLE 1034-(N-2-(Piperidin-1-yl)ethyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3109]

[3110] TLC: Rf 0.48 (methanol:ethyl acetate:triethylamine=2:8:0.5);

[3111] NMR (CD₃OD+D₂O (4 drops)): δ 8.16 (d, J=7.5 Hz, 1H), 7.90 (t,J=7.5 Hz, 1H), 7.85-7.73 (m, 4H), 7.64-7.55 (m, 2H), 6.18-6.10 (m, 1H),4.93 (d, J=14.4 Hz, 1H), 4.60 (d, J=14.4 Hz, 1H), 4.03 (dd, J=15.6, 9.0Hz, 1H), 3.84 (dd, J=15.6, 0.9 Hz, 1H), 3.72-3.00 (m, 8H), 2.74 (s, 3H),2.00-1.55 (m, 6H).

EXAMPLE 103 (1)4-(2-(N-Ethyl-N-3-methylphenyl)aminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene2hydrochloride

[3112]

[3113] TLC: Rf 0.45 (ethyl acetate:triethylamine=6:0.5);

[3114] NMR (DMSO-d₆): δ 9.64 (brs, 2H), 8.21 (d, J=6.3 Hz, 1H),7.89-7.74 (m, 5H), 7.67-7.58 (m, 2H), 7.18-7.04 (m, 1H), 6.96-6.50 (m,3H), 6.46 (dd, J=6.9, 3.0 Hz, 1H), 4.73-4.59 (m, 1H), 4.49-4.35 (m, 1H),3.97-3.80 (m, 2H), 3.80-3.58 (m, 2H), 3.50-3.33 (m, 2H), 3.29-3.10 (m,2H), 2.25 (s, 3H), 1.06 (t, J=6.9 Hz, 3H).

EXAMPLE 103 (2)4-(N-Benzyl-N-ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[3115]

[3116] TLC: Rf 0.67 (ethyl acetate:triethylamine=6:0.5);

[3117] NMR (CD₃OD+pyridine-d₅) δ 7.92 (d, J=7.2 Hz, 1H), 7.71-7.58 (m,4H), 7.57-7.45 (m, 3H), 7.32-7.15 (m, 5H), 5.84 (dd, J=8.4, 1.8 Hz, 1H),4.33 (d, J=14.7Hz, 1H), 3.90-3.62 (m, 4H),3.60 (d, J=13.2 Hz, 1H), 2.65.(q, J=7.2Hz, 2H), 1.14 (t, J=7.2 Hz, 3H).

EXAMPLE 103 (3)4-(2-Diethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[3118]

[3119] TLC: Rf 0.35 (methanol ethyl acetate triethylamine=2:8:0.5);

[3120] NMR (DMSO-d₆): δ 10.66 (brs, 1H), 9.96 (brs, 1H), 9.76 (brs, 1H),8.26-8.26 (m, 1H), 7.91-7.74 (m, 5H), 7.67-7.57 (m, 2H), 6.54-6.45 (m,1H), 4.83-4.65 (m, 1H), 4.60-4.42 (m, 1H), 3.96-3.82 (m, 2H), 3.70-3.37(m, 4H), 3.28-3.10 (m, 4H), 1.26 (t, J=7.2 Hz, 6H).

EXAMPLE 103 (4)4-(4-Methylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3121]

[3122] TLC: Rf 0.47 (ethyl acetate:triethylamine=6:0.5);

[3123] NMR (DMSO-d₆): δ 9.83 (brs, 1H), 9.54 (brs, 1H), 8.16 (d, J=6.9Hz, 1H), 7.89-7.75 (m, 3H), 7.75-7.68 (m, 2H), 7.68-7.59 (m, 2H), 7.50(d, J=8.1 Hz, 2H), 7.25 (d, J=8.1 Hz, 2H), 6.29 (dd, J=4.8, 3.9 Hz, 1H),4.72-4.58 (m, 1H), 4.44-4.32 (m, 1H), 4.25 (brs, 2H), 3.93-3.80 (m, 2H),2.32 (s, 3H).

EXAMPLE 103 (5)4-(N-Ethyl-N-2-(piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3124]

[3125] TLC: Rf 0.47 (methanol ethyl:acetate triethylamine=2:8:0.5);

[3126] NMR (CD₃OD+D₂O (1 drop)) δ 8.24 (d, J=7.5 Hz, 1H), 7.92-7.69 (m,5H), 7.61-7.52 (m, 2H), 6.21-6.10 (m, 1H), 5.15 (d, J=14.4 Hz, 1H), 4.70(d, J=14.4 Hz, 1H), 4.05 (dd, J=15.3, 9.0 Hz, 1H), 3.84 (dd, J=15.3, 0.9Hz, 1H), 3.76-2.80 (m, 10H), 1 98-1.50 (m, 6H), 1.45 (t, J=7.2 Hz, 3H).

EXAMPLE 103 (6)4-(2-Methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3127]

[3128] TLC: Rf 0.49 (ethyl acetate:triethylamine=6:0.5);

[3129] NMR (DMSO-d₆): δ 9.51 (brs, 2H), 8.21-8.11 (m, 1H), 7.89-7.775(m, 3H), 7.74-7.58 (m, 4H), 7.51 (d, J=7.5 Hz, 1H), 7.47-7.38 (m, 1H),7.08 (d, J=8.1 Hz, 1H), 7.01 (t, J=7.5 Hz, 1H), 6.16-6.06 (m, 1H),4.77-4.62 (m, 1H), 4.52-4.37 (m, 1H), 4.31-4.12 (m, 2H), 3.95-3.82 (m,2H), 3.81 (s, 3H).

EXAMPLE 103 (7)4-(3-Phenylpropyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3130]

[3131] TLC: Rt 0.37 (ethyl acetate:triethylamine=6:0.5);

[3132] NMR (DMSO-d₆): δ 9.50 (brs, 1H), 8.16 (d, J=6.3 Hz, 1H),7.90-7.73 (m, 5H), 7.68-7.58 (m, 2H), 7.35-7.16 (m, 5H), 6.44 (dd,J=6.9, 3.0 Hz, 1H), 4.69-4.54 (m, 1H), 4.45-4.31 (m , 1H), 3.95-3.79 (m,2H), 3.14-2.95 (m, 2H), 2.68 (t, J=7.2 Hz, 2H), 2.09-1.91 (m, 2H).

EXAMPLE 103 (8)4-(3,5-Dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3133]

[3134] TLC: Rf 0.43(ethyl acetate:triethylamine=6:0.5);

[3135] NMR (DMSO-d₆): δ 9.94 (brs, 1H), 9.65 (brs, 1H), 8.17 (d, J=6.9Hz, 1H), 7.90-7.75 (m, 3H), 7.75-7.67 (m, 2H), 7.67-7.58 (m, 2H), 6.87(d, J=2.1 Hz, 2H), 6.55 (t, J=2.1 Hz, 1H), 6.30 (t, J=4.5 Hz, 1H),4.72-4.57 (m, 1H), 4.43-4.28 (m, 1H), 4.23 (brs, 2H), 4.00-3.67 (m, 2H),3.75 (s, 6H).

EXAMPLE 103 (9)4-((3R)-1-Benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3136]

[3137] TLC: Rf 0.45(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3138] NMR (CD₃OD): δ 8.20 (d, J=6.9 Hz, 1H), 7.91-7.70 (m, 5H),7.66-7.54 (m, 4H), 7.53-7.43 (m, 3H), 6.18-6.05 (m, 1H), 4.77 (d, J=14.1Hz, 1H), 4.67-4.32 (m, 4H), 4.02-3.66 (m, 5H), 3.62-3.38 (m, 1H),2.88-2.40 (m, 2H).

EXAMPLE 103 (10)4-((3S)-1-Benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene2hydrochloride

[3139]

[3140] TLC: Rf 0.45(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3141] NMR (CD₃OD): δ 8.20 (d, J=6.9 Hz, 1H), 7.91-7.70 (m, 5H),7.66-7.54 (m, 4H), 7.53-7.43 (m, 3H), 6.18-6.04 (m, 1H), 4.78 (d, J=12.9Hz, 1H), 4.68-4.32 (m, 4H), 4.02-3.66 (m, 5H), 3.62-3.38 (m, 1H),2.88-2.40 (m, 2H).

EXAMPLE 103 (11)4-(2-Phenylethyl)aminomethyl-3-phenylsulfonyl-2,3-dohydro-1,1-dioxidebenzo[b]thiophene

[3142]

[3143] Free Compound:

[3144] TLC: Rf 0.28 (ethyl acetate);

[3145] NMR (CDCl₃): δ 7.65-7.40 (m, 8H), 7.30-7.15 (m, 5H), 5.90 (dd,J=9.3, 0.9 Hz, 1H), 4.66 (d, J=14.2 Hz, 1H), 3.92 (d, J=14.2 Hz, 1H),3.73 (dd, J=15.0, 0.9 Hz, 1H), 3.42 (dd, J=15.0, 9.3 Hz, 1H), 3.01-2.74(m, 4H).

[3146] Hydrochloride:

[3147] TLC: Rf 0.28 (ethyl acetate);

[3148] NMR (DMSO-d₆): δ 9.55 (br, 1H), 9.35 (br, 1H), 8.18 (dd, J=6.2,2.5 Hz, 1H), 7.94-7.87 (m, 2H), 7.82-7.78 (m, 3H), 7.67-7.62 (m, 2H),7.38-7.33 (m, 2H), 7.29-7.25 (m, 3H), 6.41 (dd, J=7.5, 2.1 Hz, 1H),4.69-4.6 5 (m, 1H), 4.45-4.41 (m, 1H), 3.92 (dd, J=15.3, 7.5 Hz, 1H),3.84 (dd, J=15.3, 2.1 Hz, 1H), 3.32-3.25 (m, 2H), 3,08-2.98 (m, 2H).

EXAMPLE 103 (12)4-(N-Benzyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3149]

[3150] Free Compound:

[3151] TLC: Rf 0.42 (hexane:ethyl acetate=1:2);

[3152] NMR (CDCl₃): δ 7.71 (dd, J=7.2,1.2 Hz, 1H), 7.64-7.49 (m, 5H),7.44-7.39 (m, 2H), 7.34-7.20 (m, 5H), 6.08 (dd, J=9.3, 1.0 Hz, 1H), 4.66(d, J=14.1 Hz, 1H), 3.88 (dd, J=15.0, 1.0 Hz, 1H), 3.69 (dd, J=15.0, 9.3Hz, 1H), 3.61 (d, J=12.9 Hz, 1H), 3.53 (d, J=14.1 Hz, 1H), 3.47 (d,J=12.9 Hz, 1H), 2.16 (s, 3H).

[3153] Hydrochloride:

[3154] TLC: Rf 0.42 (hexane:ethyl acetate=1:2);

[3155] NMR (CD₃OD+pyridine-d₅): δ 7.92 (d, J=7.5 Hz, 1H), 7.73-7.63 (m,5H), 7.56-7.50 (m, 2H), 7.37-7.31 (m, 5H), 5.99 (dd, J=7.0, 3.0 Hz, 1H),4.52 (d, J=14.4 Hz, 1H), 3.94-3.85 (m, 3H), 3.83 (d, J=13.0 Hz, 1H),3.76 (d, J=13.0 Hz, 1H), 2.32 (s, 3H).

EXAMPLE 103 (13)4-(3-(2-Oxopyrrolidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3156]

[3157] Free Compound:

[3158] TLC: Rf 0.27 (ethyl acetate:methanol:triethylamine=8:1:1);

[3159] NMR (CDCl₃): δ 7.72 (dd, J=7.5, 1.5 Hz, 1H), 7.65-7.54 (m, 4H),7.51 (dd, J=7.5, 1.5 Hz, 1H), 7.47-7.42 (m, 2H), 5.98 (t-like, J=5.1 Hz,1H), 4.56 (d, J=13.8 Hz, 1H), 3.91-3.87 (m, 3H), 3.40-3.30 (m, 4H),2.67-2.53 (m, 2H), 2.41-2.38 (m, 2H), 2.05-1.95 (m, 2H), 1.78-1.69 (m,2H).

[3160] Hydrochloride:

[3161] TLC: Rf 0.27 (ethyl acetate:methanol:tiethylamine=8:1:1);

[3162] NMR (DMSO-d₆): δ 9.32 (m, 1H), 9.08 (m, 1H), 8.14 (dd, J=6.3, 2.1Hz, 1H), 7.90-7.78 (m, 5H), 7.67-7.62 (m, 2H), 6.40 (dd, J=7.5, 2.0 Hz,1H), 4.66-4.60 (m, 1H), 4.43-4.37 (m, 1H), 3.94-3.81 (m, 2H), 3.38-3.25(m, 4H), 3.03-2.97 (m, 2H), 2.26 (t, J=8.0 Hz, 2H), 1.99-1.83 (m, 4H).

EXAMPLE 103 (14)4-(4-Aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3163]

[3164] Free Compound:

[3165] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:1:1);

[3166] NMR (DMSO-d₆): δ 7.90 (dd, J=7.0, 2.0 Hz, 1H), 7.80-7.61 (m, 7H),6.97 (d, J 8.5 Hz, 2H), 6.52 (d, J=8.5 Hz, 2H), 5.81 (dd, J=8.0, 1.8 Hz,1H), 4.93 (s, 2H), 4.01 (d, J=14.7 Hz, 1H), 3.91 (dd, J=15.0, 8.0 Hz,1H), 3.84 (dd, J=15.0, 1.8 Hz, 1H), 3.77 (d, J=14.7 Hz, 1H), 3.48 (s,2H).

[3167] Hydrochloride:

[3168] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:1:1);

[3169] NMR (DMSO-d₆): δ 9.90 (br, 1H), 9.59 (br, 1H), 8.18 (dd, J=7.0,1.5 Hz, 1H), 7.88-7.60 (m, 9H), 7.21 (d, J=7.8 Hz, 2H), 6.37-6.34 (m,1H), 4.70-4.64 (m, 1H), 4.42-4.32 (m, 1H), 4.28 (s, 2H), 3.93-3.82 (m,2H).

EXAMPLE 103 (15)4-(4-((2E)-3-Phenyl-2-propenyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3170]

[3171] Free Compound:

[3172] TLC: Rf 0.48 (ethyl acetate:methanol=9:1);

[3173] NMR (CDCl₃): δ 7.65-7.20 (m, 13H), 6.52 (d, J=15.9 Hz, 1H), 6.30(dd, J=9.3, 1.2 Hz, 1H), 6.26 (dt, J=15.9, 6.8 Hz, 1H), 4.70 (d, J=14.3Hz, 1H), 3.91 (dd, J=15.0, 1.2 Hz, 1H), 3.73 (dd, J=15.0, 9.3 Hz, 1H),3.42 (d, J=14.3 Hz, 1H), 3.16 (d, J=6.8 Hz, 2H), 2.60-2.40 (m, 8H).

[3174] Hydrochloride:

[3175] TLC: Rf 0.48 (ethyl acetate:methanol=9:1);

[3176] NMR (CD₃OD+D₂O): 5 7.93 (d, J=7.0 Hz, 1H), 7.78-7.72 (m, 4H),7.66 (d, J=7.0 Hz, 1H), 7.61-7.50 (m, 2H), 7.41-7.33 (m, 3H), 6.95 (d,J=15.6 Hz, 1H), 6.33 (dt, J=15.6, 7.7 Hz, 1H), 6.16 (d, J=9.0 Hz, 1H),4.54 (d, J=14.5 Hz, 1H), 4.02 (dd, J=15.0,9.0Hz, 1H), 3.96 (d, J=7.7Hz,2H), 3.89 (d, J=15.0Hz, 1H), 3.85 (d, J=14.5 Hz, 1H), 3.42 (br, 4H),3.29 (br, 4H).

EXAMPLE 103 (16)4-(2-Aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3177]

[3178] Free Compound:

[3179] TLC: Rf 0.30 (ethyl acetate);

[3180] NMR (CDCl₃): δ 7.74 (d, J=7.5 Hz, 1H), 7.65-7.55 (m, 2H),7.51-7.39 (m, 5H), 7.09 (dt, J=7.5, 1.5 Hz, 1H), 6.97 (dd, J=7.5, 1.5Hz, 1H), 6.67 (dt, J=7.5, 1.5 Hz, 1H), 6.63 (dd, J=7.5, 1.5 Hz, 1H),5.43 (dd, J=9.5, 1.2 Hz, 1H), 4.29 (d, J=14.3 Hz, 1H), 4.02 (d, J=14.3Hz, 1H), 3.88 (d, J=12.6 Hz, 1H), 3.82 (dd, J=15.0, 1.2 Hz, 1H), 3.81(d, J=12.6 Hz, 1H), 3.66 (dd, J=15.0, 9.5 Hz, 1H).

[3181] Hydrochloride:

[3182] TLC: Rf 0.30 (ethyl acetate); NMR (DMSO-d₆): δ 8.17 (dd, J=6.3,2.4 Hz, 1H), 7.87-7.71 (m, 5H), 7.66-7.61 (m, 2H), 7.50 (br, 2H), 7.29(dd, J=7.5, 1.2 Hz, 1H), 7.13 (dt, J=7.5, 1.2 Hz, 1H), 6.75 (d, J=7.5Hz, 1H), 6.63 (t, J=7.5 Hz, 1H), 6.21 (t-like, J=5.0 Hz, 1H), 4.72 (d,J=13.8 Hz, 1H), 4.46 (d, J=13.8 Hz, 1H), 4.26-4.17 (m, 2H), 3.93-3.82(m, 2H).

EXAMPLE 103 (17)4-(4-Benzylpiperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3183]

[3184] Free Compound:

[3185] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[3186] NMR (CDCl₃) δ 7.66-7.56 (m, 4H), 7.53-7.51 (m, 2H), 7.48-7.43 (m,2H), 7.30-7.25 (m, 2H), 7.21-7.11 (m, 3H), 6.36 (d, J=9.3 Hz, 1H), 4.62(d, J=14.4 Hz, 1H), 3.89 (d, J=15.0 Hz, 1H), 3.71 (dd, J=15.0, 9.3 Hz,1H), 3.35 (d, J=14.4 Hz, 1H), 3.04-3.00 (m, 1H), 2.53 (d, J=6.9 Hz, 2H),2.55-2.50 (m, 1H), 2.05 (dt, J=11.5, 2.5 Hz, 1H), 1.85 (dt, J=11.5, 2.5Hz, 1H), 1.74-1.68 (m, 1H), 1.62-1.15 (m, 2H), 1.35 (dt, J=12.0, 3.5 Hz,1H), 1.16-1.02 (m, 1H).

[3187] Hydrochloride:

[3188] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[3189] NMR (DMSO-d₆): δ 10.42 (br, 1H), 8.22 (d, J=7.0 Hz, 1H),7.92-7.72 (m, 5H), 7.65-7.60 (m, 2H), 7.31-7.15 (m, 5H), 6.30 (d, J=9.0Hz, 1H), 4.72 (dd, J=13.8, 5.3 Hz, 1H), 4.53 (dd, J=13.8,5.3 Hz, 1H),4.02 (dd, J=15.3,9.0 Hz, 1H), 3.83 (d, J=15.3 Hz, 1H), 3.42-3.39 (m,1H), 3.12-3.00 (m, 3H), 2.60-2.42 (m, 2H), 1.79-1.49 (m, 5H).

EXAMPLE 103 (18)4-(4-Chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3190]

[3191] Free Compound:

[3192] TLC: Rf 0.43(ethyl acetate);

[3193] NMR (CDCl₃): δ 7.75 (dd, J=7.0,1.2 Hz, 1H), 7.66-7.51 (m, 5H),7.47-7.42 (m, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 5.81(dd, J=9.3,1.3 Hz, 1H), 4.48 (d, J=14.0 Hz, 1H), 3.99 (d, J=14.0 Hz,1H), 3.86 (dd, J=15.0,1.3 Hz, 1H), 3.84 (d, J=13.3 Hz, 1H), 3.78 (d,J=13.3 Hz, 1H), 3.68 (dd, J=15.0, 9.3 Hz, 1H).

[3194] Hydrochloride:

[3195] TLC: Rf 0.43 (ethyl acetate);

[3196] NMR (DMSO-d₆): δ 9.86 (br, 1H), 9.55 (br, 1H), 8.16 (dd, J=6.6,1.8 Hz, 1H), 7.88-7.72 (m, 5H), 7.67-7.62 (m, 4H), 7.53 (d, J=8.4 Hz,2H), 6.31 (dd, J=6.2, 3.5 Hz, 1H), 4.70-4.66 (m, 1H), 4.43-4.39 (m, 1H),4.32 (s, 2H), 3.90 (dd, J=15.5, 6.2 Hz, 1H), 3.84 (dd, J=15.5, 3.5 Hz,1H).

EXAMPLE 103 (19) 4-(3-Chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3197]

[3198] Free Compound:

[3199] TLC: Rf 0.51 (ethyl acetate);

[3200] NMR (CDCl₃): δ 7.76 (dd, J=7.0, 1.2 Hz, 1H), 7.67-7.40 (m, 7H),7.30-7.14 (m, 4H), 5.80 (dd, J=9.2,1.4 Hz, 1H), 4.48 (d, J=14.0 Hz, 1H),3.99 (d, J=14.0 Hz, 1H), 3.87 (dd, J=15.4, 1.4 Hz, 1H), 3.86 (d, J=13.6Hz, 1H), 3.77 (d, J=13.6 Hz, 1H), 3.69 (dd, J=15.4, 9.2 Hz, 1H).

[3201] Hydrochloride:

[3202] TLC: Rf 0.51 (ethyl acetate);

[3203] NMR (DMSO-d₆): δ 9.92 (br, 1H), 9.62 (br, 1H), 8.18 (dd, J=6.6,1.8 Hz, 1H), 7.88-7.74 (m, 6H), 7.67-7.59 (m, 3H), 7.52-7.45 (m, 2H),6.39 (dd, J=5.7, 4.2 Hz, 1H), 4.74-4.69 (m, 1H), 4.44-4.40 (m, 1H), 4.35(s, 2H), 3.90 (dd, J=15.6, 5.7 Hz, 1H), 3.84 (dd, J=15.6, 4.2 Hz, 1H).

EXAMPLE 103 (20)4-(3-Methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3204]

[3205] Free Compound:

[3206] TLC: Rf 0.41 (ethyl acetate);

[3207] NMR (CDCl₃): δ 7.75 (dd, J=7.2, 1.2 Hz, 1H), 7.65-7.50 (m, 5H),7.46-7.40 (m, 2H), 7.26-7.21 (m, 1H), 6.86-6.79 (m, 3H), 5.81 (dd,J=9.3, 1.2 Hz, 1H), 4.48 (d, J=14.1 Hz, 1H), 3.98 (d, J=14.1 Hz, 1H),3.84 (d, J=13.5 Hz, 1H), 3.84 (dd, J=15.0, 1.2 Hz, 1H), 3.80 (s, 3H),3.74 (d, J=13.5 Hz, 1H), 3.66 (dd, J=15.0, 9.3 Hz, 1H).

[3208] Hydrochloride:

[3209] TLC: Rf 0.41 (ethyl acetate);

[3210] NMR (DMSO-d₆): δ 9.83 (br, 1H), 9.55 (br, 1H), 8.16 (dd, J=6.6,1.8 Hz, 1H), 7.89-7.78 (m, 3H), 7.73-7.61 (m, 4H), 7.36 (t, J=7.9 Hz,1H), 7.30 (d, J=2.5 Hz, 1H), 7.15 (d, J=7.9Hz, 1H), 7.00 (dd,J=7.9,2.5Hz, 1H), 6.27 (dd, J=6.0,3.9Hz, 1H), 4.70-4.65 (m, 1H),4.42-4.37 (m,1H), 4.29 (br, 2H), 3.89 (dd, J=15.5, 6.0 Hz, 1H), 3.84(dd, J=15.5, 3.9 Hz, 1H), 3.78 (s, 3H).

EXAMPLE 103 (21)4-(3,4-Dichlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3211]

[3212] Free Compound:

[3213] TLC: Rf 0.42(ethyl acetate);

[3214] NMR (CDCl₃): δ 7.77 (dd, J=7.2, 1.2 Hz, 1H), 7.67-7.52 (m, 5H),7.47-7.39 (m, 4H), 7.15 (dd, J=8.3, 2.0 Hz, 1H), 5.76 (dd, J=9.5, 1.2Hz, 1H), 4.45 (d, J=13.8 Hz, 1H), 4.00 (d, J=13.8 Hz, 1H), 3.86 (dd,J=15.0, 1.2 Hz, 1H), 3.84 (d, J=13.8 Hz, 1H), 3.78 (d, J=13.8 Hz, 1H),3.70 (dd, J=15.0, 9.5 Hz, 1H).

[3215] Hydrochloride:

[3216] TLC: Rf 0.42 (ethyl acetate);

[3217] NMR (DMSO-d₆): δ 9.94 (br, 1H), 9.62 (br, 1H), 8.17 (dd, J=6.6,2.1 Hz, 1H), 7.96 (d, J=1.8 Hz,1H), 7.89-7.73 (m, 6H), 7.67-7.60 (m,3H), 6.40 (dd, J=5.5, 4.2 Hz, 1H), 4.75-4.68 (m, 1H), 4.45-4.40 (m, 1H),4.35 (s, 2H), 3.95 (dd, J=15.5, 5.5 Hz, 1H), 3.85 (dd, J=15.5, 4.2 Hz,1H).

EXAMPLE 103 (22)4-(1,3-Dioxaindan-5-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3218]

[3219] Free Compound:

[3220] TLC: Rf 0.43(ethyl acetate);

[3221] NMR (CDCl₃): δ 7.73 (dd, J=7.5, 1.2 Hz, 1H), 7.65-7.49 (m, 5H),7.46-7.41 (m, 2H), 6.77 (d, J=1.5 Hz,1H), 6.74 (d, J=8.0 Hz, 1H), 6.69(dd, J=8.0, 1.5 Hz, 1H), 5.95-5.94 (m, 2H), 5.88 (dd, J=9.5,1.0 Hz, 1H),4.50 (d, J=14.0 Hz,1H), 3.96 (d, J=14.0 Hz, 1H), 3.86 (dd, J=15.0, 1.0Hz, 1H), 3.77 (d, J=13.0 Hz, 1H), 3.68 (d, J=13.0 Hz, 1H), 3.68 (dd,J=15.0, 9.5 Hz, 1H).

[3222] Hydrochloride:

[3223] TLC: Rf 0.43 (ethyl acetate);

[3224] NMR (DMSO-d₆): δ 9.78 (br, 1H), 9.47 (br, 1H), 8.15 (dd, J=6.6,1.8 Hz, 1H), 7.88-7.72 (m, 5H), 7.66-7.61 (m, 2H), 7.25 (d, J=1.5 Hz,1H), 7.08 (dd, J=7.8, 1.5 Hz, 1H), 6.99 (d, J=7.8 Hz, 1H), 6.30 (t-like,J=4.5 Hz, 1H), 6.05 (s, 2H), 4.67-4.61 (m, 1H), 4.38-4.33 (m, 1H), 4.23(s, 2H), 3.93-3.83 (m, 2H).

EXAMPLE 103 (23)4-(2,3-Dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3225]

[3226] Free Compound:

[3227] TLC: Rf 0.36(ethyl acetate);

[3228] NMR (CDCl₃): δ 7.71 (dd, J=7.0, 1.3 Hz, 1H), 7.63-7.48 (m, 5H),7.45-7.39 (m, 2H), 7.00 (t, J=7.8 Hz, 1H), 6.84 (dd, J=7.8, 1.5 Hz, 1H),6.78 (dd, J=7.8, 1.5 Hz, 1H), 6.06 (dd, J=9.3, 1.3 Hz, 1H), 4.52 (d,J=14.1 Hz, 1H), 3.92 (d, J=14.1 Hz, 1H), 3.86 (s, 3H), 3.85 (dd, J=15.0,1.3 Hz, 1H), 3.80 (d, J=13.3 Hz, 1H), 3.76 (s, 3H), 3.73 (dd, J=15.0,9.3 Hz, 1H), 3.69 (d, J=13.3 Hz, 1H).

[3229] Hydrochloride:

[3230] TLC: Rf 0.36 (ethyl acetate);

[3231] NMR (DMSO-d₆): δ 9.70-9.60 (br, 2H), 8.17 (dd, J=6.6, 2.1 Hz,1H), 7.89-7.73 (m, 5H), 7.67-7.62 (m, 2H), 7.25-7.21 (m, 1H), 7.15-7.13(m, 2H), 6.12 (dd, J=6.8, 2.5 Hz, 1H), 4.71-4.67 (m, 1H), 4.45-4.41 (m,1H), 4.32-4.20 (m, 2H), 3.93-3.83 (m, 2H), 3.83 (s, 3H), 3.80 (s, 3H).

EXAMPLE 103 (24)4-(3,4,5-Trimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3232]

[3233] Free Compound:

[3234] TLC: Rf 0.20(ethyl acetate);

[3235] NMR (CDCl₃): δ 7.79 (dd, J=7.2, 1.2 Hz, 1H), 7.66-7.52 (m, 5H),7.47-7.42 (m, 2H), 6.54 (s, 2H), 5.72 (dd, J=9.3, 1.2 Hz, 1H), 4.45 (d,J=14.0 Hz, 1H), 4.03 (d, J=14.0 Hz, 1H), 3.86 (s, 6H), 3.84 (s, 3H),3.84 (dd, J=15.0, 1.2 Hz, 1H), 3.82 (d, J=13.5 Hz, 1H), 3.74 (d, J=13.5Hz, 1H), 3.66 (dd, J=15.0, 9.3 Hz, 1H).

[3236] Hydrochloride:

[3237] TLC: Rf 0.20 (ethyl acetate);

[3238] NMR (DMSO-d₆): δ 9.98 (br, 1H), 9.63 (br, 1H), 8.18 (dd, J=6.6,1.5 Hz, 1H), 7.89-7.78 (m, 3H), 7.72-7.60 (m, 4H), 7.06 (s, 2H), 6.30(dd, J=6.0, 3.5 Hz, 1H), 4.69-4.66 (m, 1H), 4.39-4.37 (m, 1H), 4.24 (s,2H), 3.92-3.84 (m, 2H), 3.80 (s, 6H), 3.67 (s, 3H).

EXAMPLE 103 (25)4-(4-(t-Butyloxycarbonyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3239]

[3240] Free Compound:

[3241] TLC: Rf 0.49 (hexane:ethyl acetate=1:2);

[3242] NMR (CDCl₃): δ 7.66-7.52 (m, 6H), 7.48-7.43 (m, 2H), 6.18 (dd,J=9.0, 1.0 Hz, 1H), 4.69 (d, J=14.3 Hz, 1H), 3.89 (dd, J=15.0, 1.0 Hz,1H), 3.72 (dd, J=15.0, 9.0 Hz, 1H), 3.49-3.35 (m, 4H), 3.45 (d, J=14.3Hz, 1H), 2.52-2.45 (m, 2H), 2.36-2.29 (m, 2H), 1.46 (s, 9H).

[3243] Hydrochloride:

[3244] TLC: Rf 0.49 (hexane:ethyl acetate=1:2);

[3245] NMR (CD₃OD): δ 8.11 (d, J=7.2 Hz, 1H), 7.92-7.83 (m, 2H),7.77-7.73 (m, 3H), 7.60-7.55 (m, 2H), 6.03 (dd, J=8.7, 1.0 Hz, 1H), 5.01(d, J=14.3 Hz, 1H), 4.71 (d, J=14.3 Hz, 1H), 4.22 (br, 2H), 3.99 (dd,J=15.3, 8.7 Hz, 1H), 3.84 (dd, J=15.3,1.0 Hz, 1H), 3.65-3.25 (br, 6H),1.47 (s, 9H).

EXAMPLE 103 (26)4-(2-Diisopropylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3246]

[3247] TLC: Rf 0.43(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3248] NMR (CD₃OD+D₂O): δ 8.18 (d, J=7.5 Hz, 1H), 7.97-7.76 (m, 5H),7.70-7.60 (m, 2H), 6.20-6.12 (m, 1H), 4.85 (d, J=13.8 Hz, 1H); 4.67 (d,J=13.8 Hz, 1H), 4.01-3.50 (m, 8H), 1.44(d, J=6.3 Hz, 12H).

EXAMPLE 103 (27)4-(2-(Morpholin-4-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene2hydrochloride

[3249]

[3250] TLC: Rf 0.37(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3251] NMR (CD₃OD+D₂O): δ 8.18 (d, J=7.5 Hz, 1H), 7.97-7.76 (m, 5H),7.69-7.60 (m, 2H), 6.17-6.10 (m, 1H), 4.86 (d, J=13.8 Hz, 1H), 4.69 (d,J=13.8 Hz, 1H), 4.05-3.90 (m, 5H), 3.89-3.71 (m, 3H), 3.67-3.53 (m, 2H),3.5 1-3.33 (m, 4H).

EXAMPLE 103 (28)4-(N-2-(Piperidin-1-yl)ethyl-N-propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3252]

[3253] Free Compound:

[3254] TLC: Rf 0.51 (ethyl acetate:triethylamine 9:1);

[3255] NMR (CDCl₃): δ 7.68 (d, J=7.2 Hz, 1H), 7.64-7.46 (m, 5H),7.44-7.39 (m, 2H), 6.29 (dd, J=9.3, 1.2 Hz, 1H), 4.69 (d, J=14.4 Hz,1H), 3.90 (dd, J=15.0, 1.2 Hz, 1H), 3.72 (dd, J=15.0, 9.3 Hz, 1H), 3.58(d, J=14.4 Hz, 1H), 2.70-2.30 (m, 10H), 1.57-1.38 (m, 8H), 0.79 (t,J=7.2 Hz, 3H).

Hydrochloride:

[3256] TLC: Rf 0.51 (ethyl acetate:triethylamine=9:1);

[3257] NMR (CD₃OD+pyridine-d₅): δ 7.93 (d, J=7.2 Hz, 1H), 7.74-7.68 (m,4H), 7.61-7.52 (m, 3H), 6.01 (dd, J=8.7,1.2 Hz, 1H), 4.38 (d, J=14.7 Hz,1H), 3.99 (dd, J=15.3, 8.7 Hz, 1H), 3.89 (dd, J=15.3, 1.2 Hz, 1H), 3.85(d, J=14.7 Hz, 1H), 3.27-3.22 (m, 2H), 3.14 (br, 4H), 2.97-2.81 (m, 2H),2.61-2.45 (m, 2H), 1.85-1.77 (m, 4H), 1.65-1.53 (m, 4H), 0.89 (t, J=7.3Hz, 3H).

EXAMPLE 103 (29)4-(N-2-(Piperidin-1-yl)ethyl-N-isopropyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3258]

[3259] Free Compound:

[3260] TLC: Rf 0.48 (ethyl acetate:triethylamine=9:1);

[3261] NMR (CDCl₃): δ 7.77 (d, J=7.2 Hz, 1H), 7.65-7.47 (m, 5H),7.45-7.40 (m, 2H), 6.09 (d, J=9.0, 1.0 Hz, 1H), 4.54 (d, J=15.0 Hz, 1H),3.88 (dd, J=15.0, 1.0 Hz, 1H), 3.74 (d, J=15.0 Hz, 1H), 3.73 (dd,J=15.0, 9.0 Hz, 1H), 2.84 (sept, J=6.6 Hz, 1H), 2.57-2.51 (m, 2H),2.38-2.17 (m, 6H), 1.55-1.48 (m, 4H), 1.42-1.35 (m, 2H), 1.06 (d, J=6.6Hz, 3H), 1.03 (d, J=6.6 Hz, 3H).

[3262] Hydrochloride:

[3263] TLC: Rf 0.48 (ethyl acetate:triethylamine=9:1);

[3264] NMR (CD₃OD+pyridine-d₅): δ 7.99 (d, J=7.5 Hz, 1H), 7.75-7.70 (m,4H), 7.61-7.54 (m, 3H), 5.93 (dd, J=8.7, 1.5 Hz, 1H), 4.27 (d, J=15.6Hz, 1H), 3.99 (dd, J=15.3, 8.7 Hz, 1H), 3.96 (d, J=15.6 Hz, 1H), 3.88(dd, J=15.3, 1.5 Hz, 1H), 3.20-2.80 (m, 9H), 1.82-1.75 (m, 4H),1.63-1.58 (m, 2H), 1.17-1.14 (m, 6H).

EXAMPLE 103 (30)4-(3,4-Dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3265]

[3266] Free Compound:

[3267] TLC: Rf 0.19 (ethyl acetate);

[3268] NMR (CDCl₃): δ 7.76 (dd, J=7.2, 1.0 Hz, 1H), 7.65-7.51 (m, 5H),7.46-7.41 (m, 2H), 6.84-6.82 (m, 3H), 5.79 (d, J=9.3 Hz, 1H), 4.47 (d,J=14.0 Hz, 1H), 4.00 (d, J=14.0 Hz, 1H), 3.87 (s, 6H), 3.85 (d, J=15.0Hz, 1H), 3.82 (d, J=13.2 Hz, 1H), 3.73 (d, J=13.2 Hz, 1H), 3.66 (dd,J=15.0, 9.3 Hz, 1H).

[3269] Hydrochloride:

[3270] TLC: Rf 0.19 (ethyl acetate);

[3271] NMR (DMSO-d₆): δ 10.00-9.70 (br, 2H), 8.38-8.28 (m, 1H),8.06-7.94 (m, 3H), 7.88-7.76 (m, 4H), 7.56 (d, J=1.4 Hz, 1H), 7.27 (dd,J=8.4, 1.4 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 6.43-6.38 (m, 1H), 4.80 (d,J=12.8 Hz, 1H), 4.53 (d, J=12.8 Hz, 1H), 4.40 (s, 2H), 4.13-4.00 (m,2H), 3.94 (s, 6H).

EXAMPLE 103 (31)4-(3-(2-Methylpiperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3272]

[3273] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=8:2:0.5);

[3274] NMR (CD₃OD): δ 8.18 (d, J=7.2 Hz, 1H), 7.92-7.73 (m, 5H),7.67-7.57 (m, 2H), 6.22-6.23 (m, 1H), 4.80 (d, J=13.5 Hz, 1H), 4.62 (d,J=13.5 Hz, 1H), 3.98-3.91 (m, 1H), 3.83-3.74 (m, 1H), 3.64-2.98 (m, 7H),2.37-2.17 (m, 2H), 2.07-1.52 (m, 6H), 1.41 (d, J=6.3 Hz, 3H).

EXAMPLE 103 (32)4-(4-(Piperidin-1-yl)piperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3275]

[3276] TLC: Rf 0.41 (ethyl acetate methanol:triethylamine=8:2:0.5);

[3277] NMR (D₂O): δ 8.17-8.08 (m, 1H), 8.03-7.94 (m, 2H), 7.91-7.82 (m,1H), 7.79-7.73 (m, 2H), 7.72-7.62 (m, 2H), 4.71 (d, J=14.4 Hz, 1H), 4.65(d, J=14.4 Hz, 1H), 4.21-4.05 (m, 2H), 3.87-3.75 (m, 1H), 3.69-3.48 (m,4H), 3.38-2.98 (m, 4H), 2.52-2.32 (m, 2H), 2.19-1.93 (m, 4H), 1.91-1.65(m, 3H), 1.59-1.40 (m, 1H).

EXAMPLE 103 (33)4-(3-(Piperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3278]

[3279] TLC: Rf 0.25 (methanol:ethyl acetate:triethylamine=2:8:0.5);

[3280] NMR (CD₃OD+D₂O) δ 8.16 (d, J=7.2 Hz, 1H), 7.95-7.74 (m, 5H),7.69-7.59 (m, 2H), 6.17-6.08 (m, 1H), 4.78 (d, J=14.1 Hz, 1H), 4.62 (d,J=14.1 Hz, 1H), 4.02-3.88 (m, 1H), 3.85-3.73 (m, 1H), 3.73-2.76 (m, 8H),2.3 8-2.21 (m, 2H), 2.14-1.44 (m, 6H).

EXAMPLE 103 (34)4-(3-Bromobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3281]

[3282] TLC: Rf 0.50 (ethyl acetate:triethylamine 6:0.5);

[3283] NMR (DMSO-d₆): δ 9.83 (brs, 1H), 9.56 (brs, 1H), 8.16 (d, J=6.6Hz, 1H), 7.90-7.70 (m, 6H), 7.68-7.58 (m, 4H), 7.41 (t, J=7.5 Hz, 1H),6.41-6.28 (m, 1H), 4.80-4.60 (m, 1H), 4.52-4.22 (m, 3H), 3.96-3.80 (m,2H).

EXAMPLE 103 (35)4-(4-Nitrobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophenehydrochloride

[3284]

[3285] TLC: Rf 0.34 (ethyl acetate:triethylamine=6:0.5);

[3286] NMR (DMSO-d₆): δ 10.05 (brs, 1H), 9.79 (brs, 1H), 8.29 (d, J=8.1Hz, 2H), 8.18 (d, J=6.6 Hz, 1H), 7.94-7.70 (m, 7H), 7.67-7.57 (m, 2H),6.48-6.33 (m, 1H), 4.83-4.64 (m, 1H), 4.59-4.35 (m, 3H), 3.95-3.81 (m,2H).

EXAMPLE 103 (36)4-(4-Aminosulfonylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3287]

[3288] Free Compound:

[3289] TLC: Rf 0.40 (ethyl acetate:methanol=9:1);

[3290] NMR (DMSO-d₆): δ 7.93 (dd, J=7.0, 1.5 Hz, 1H), 7.79-7.66 (m, 7H),7.63-7.58 (m, 2H), 7.53 (d, J=8.0 Hz, 2H), 7.31 (s, 2H), 5.93 (dd,J=8.3, 1.5 Hz, 1H), 4.07 (d, J=14.1 Hz,1H), 3.95 (dd, J=15.0, 8.3 Hz,1H), 3.87 (dd, J=15.0, 1.5 Hz, 1H), 3.82 (d, J=14.1 Hz, 1H), 3.75 (s,2H), 2.86 (br, 1H).

[3291] Hydrochloride:

[3292] TLC: Rf 0.40 (ethyl acetate:methanol=9:1);

[3293] NMR (DMSO-d₆): δ 9.80 (br, 1H), 9.52 (br, 1H), 8.15 (d, J=7.0 Hz,1H), 7.89-7.74 (m, 9H), 7.67-7.62 (m, 2H), 7.44 (s, 2H), 6.37-6.32 (m,1H), 4.78-4.70 (m, 1H), 4.47-4.41 (m, 1H), 4.41 (s, 2H), 3.96-3.84 (m,2H).

EXAMPLE 103 (37) 4-(Piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3294]

[3295] TLC: Rf 0.10 (ethyl acetate:methanol triethylamine=8:2:1);

[3296] NMR (CD₃OD+D₂O): δ 7.96 (d, J=7.8 Hz, 1H), 7.80-7.67 (m, SH),7.61-7.56 (m, 2H), 6.16 (dd, J=9.0, 1.3 Hz, 1H), 4.60 (d, J=14.5 Hz,1H), 4.01 (dd, J=15.4, 9.0 Hz, 1H), 3.95 (d, J=14.5 Hz, 1H), 3.89 (dd,J=15.4, 1.3 Hz, 1H), 3.37-3.33 (m, 4H), 2.98-2.90 (m, 4H).

EXAMPLE 103 (38)4-(2,4,6-Trimethoxybenzyl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3297]

[3298] Free Compound:

[3299] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[3300] NMR (CDCl₃): δ 7.69 (dd, J=7.0,1.5Hz, 1H), 7.64-7.49 (m, 5H),7.45-7.40 (m, 2H), 6.19 (dd, J=9.0,1.0 Hz, 1H), 6.12 (s, 2H), 4.50 (d,J=14.3 Hz, 1H), 3.88 (d, J=14.3 Hz, 1H), 3.85 (dd, J=15.0,1.0 Hz, 1H),3.81 (s, 3H), 3.75 (s, 6H), 3.73 (d, J=12.6 Hz, 1H), 3.65 (d, J=12.6 Hz,1H), 3.64 (dd, J=15.0, 9.0 Hz, 1H).

[3301] Hydrochloride:

[3302] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[3303] NMR (DMSO-d₆): δ 9.11 (br, 1H), 8.94 (br, 1H), 8.16-8.13 (m, 1H),7.88-7.87 (m, 2H), 7.84-7.79 (m, 1H), 7.71-7.61 (m, 4H), 6.31 (s, 2H),5.92 (dd, J=8.0,1.8 Hz, 1H), 4.66-4.62 (m, 1H), 4.39-4.34 (m, 1H),4.18-4 .13 (m, 1H), 3.97-3.91 (m, 1H), 3.92 (dd, J=15.3, 8.0 Hz, 1H),3.83 (dd, J=15.3, 1.8 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 6H).

EXAMPLE 103 (39)4-(Piperidin-1-yl)carbonylmethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3304]

Free Compound:

[3305] TLC: Rf 0.42 (ethyl acetate:methanol:triethylamine=8:1:1);

[3306] NMR (CDCl₃): δ 7.75.(dd, J=6.9, 2.1 Hz, 1H), 7.66-7.60 (m, 3H),7.58-7.53 (m, 2H), 7.48-7.43 (m, 2H), 6.13 (dd, J=9.0, 1.2 Hz, 1H), 4.61(d, J=13.8 Hz, 1H), 3.97 (d, J=13.8Hz, 1H), 3.87 (dd, J=15.0,1.2Hz, 1H),3.75 (dd, J=15.0,9.0Hz, 1H), 3.58 (t, J=5.2 Hz, 2H), 3.50 (d, J=16.0 Hz,1H), 3.41 (d, J=16.0 Hz, 1H), 3.30 (t, J=5.2 Hz, 2H), 1.69-1.55 (m, 6H).

[3307] Hydrochloride:

[3308] TLC: Rf 0.42 (ethyl acetate:methanol: triethylamine=8:1:1);

[3309] NMR (DMSO-d₆): δ 9.63 (br, 1H), 9.18 (br, 1H), 8.11 (d, J=7.2 Hz,1H), 7.93-7.80 (m, 5H), 7.70-7.64 (m, 2H), 6.28 (dd, J=6.0, 4.0 Hz, 1H),4.83 (d, J=13.2 Hz, 1H), 4.32 (d, J=13.2 Hz, 1H), 4.28-4.16 (m, 2H),3.85 (dd, J=15.3, 6.0 Hz, 1H), 3.80 (dd, J=15.3, 4.0 Hz, 1H), 3.54-3.50(m, 2H), 3.37-3.32 (m, 2H), 1.64-1.49 (m, 6H).

EXAMPLE 103 (40)4-(Pyrrolidin-1-yl)ethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene2hydrochloride

[3310]

[3311] TLC: Rf 0.22(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3312] NMR (CD₃OD+D₂O): 8.16 (d, J=7.5 Hz, 1H), 7.94-7.75 (m, 5H),7.68-7.58 (m, 2H), 6.15-6.08 (m, 1H), 4.81 (d, J=13.8 Hz, 1H), 4.63 (d,J=13.8 Hz, 1H), 4.01-3.88 (m, 1H), 3.86-3.76 (m, 1H), 3.75-3.62 (m, 4H),3.6 2-3.38 (m, 4H), 2.20-2.06 (m, 4H).

EXAMPLE 103 (41)4-(4-(1,3-Dioxaindan-5-ylmethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[3313]

[3314] TLC: Rf 0.51 (ethyl acetate:triethylamine=6:0.5);

[3315] NMR (CD₃OD+D₂O): δ 7.90 (d, J=7.5 Hz, 1H), 7.79-7.52 (m, 7H),7.04-6.96 (m, 2H), 6.95-6.87 (m, 1H), 6.15-6.07 (m, 1H), 6.01 (s, 2H),4.45 (d, J=14.4 Hz, 1H), 4.25 (s, 2H), 4.01 (dd, J=15.6, 8.7 Hz,1H),3.90 (dd, J=15.6, 1.2 Hz, 1H), 3.77 (d, J=14.4 Hz, 1H), 3.50-3.10 (br,4H), 2.98-2.63 (br, 4H).

EXAMPLE 104 4-Cyano-6,7-dihydrobenzo[b]thiophene

[3316]

[3317] To a suspension of zinc iodide (6.2 g) in acetonitrile (200 ml)were added 4-keto-4,5,6,7-tetrahydrothianaphthene (20 g) andtrimethylsilylcyanide (18 ml) successively. The mixture was stirred atroom temperature for 5 hours. The reaction mixture was concentrated. Theresidue was dissolved in pyridine (65 ml), followed by adding phosphrylchloride (15 ml) dropwise at room temperature. The mixture was refluxedfor 30 minutes. The reaction mixture was cooled with ice and thereto wasadded dropwise isopropanol. The reaction mixture was poured onto icewater and extracted with ethyl acetate. The extract was washed byhydrochloric acid, water and a saturated aqueous solution of sodiumchloride successively, dried over anhydrous magnesium sulfate andconcentrated to give the title compound (17 g) having the followingphysical data.

[3318] TLC: Rf 0.45 (hexane:ethyl acetate=3:1);

[3319] NMR (CDCl₃): δ 7.12 (d, J=5.4 Hz, 1H), 7.07 (d, J=5.4 Hz, 1H),6.62 (t, J=4.8 Hz, 1H), 2.93 (t, J=9.0 Hz, 2H), 2.60 (t, J=9.0, 4.8 Hz,2H).

EXAMPLE 105 4-Cyanobenzo[b]thiophene

[3320]

[3321] To a solution of the compound prepared in Example 104 (17 g) inbenzene (200 ml), was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(30 g). The mixture was refluxed for 1.5 hours. The mixture wasfiltered. The filtrate was concentrated. The residue was extracted witha mixed solvent (hexane:ethyl acetate=1:1). The extract was washed by anaqueous solution of sodium hydroxide, water and a saturated aqueoussolution of sodium chloride successively, dried over anhydrous magnesiumsulfate and concentrated. The residue was purified with columnchromatopgaphy on silica gel (hexane:ethyl acetate=100:1) to give thetitle compound (14.5 g) having the following physical data.

[3322] TLC: Rf 0.40 (hexane:ethyl acetate=4:1);

[3323] NMR (CDCl₃): δ 7.45 (t, J=7.5Hz, 1H), 7.60 (d, J=5.0 Hz, 1H),7.70 (d, J=5.0 Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 8.10 (d, J=7.5Hz, 1H).

EXAMPLE 106 4-Carboxybenzo[b]thiophene

[3324]

[3325] 1) To a suspension of the compound prepared in Example 105 (14.5g) in ethyleneglycol (50 ml) was added 85% potassium hydroxide (19 g).The mixture was stirred at 1 80“C for 2 hours. The reaction mixture waspoured into hydrochloric acid, and the acidic mixture was extracted withethyl acetate. The extract was washed by water and a saturated aqueoussolution of sodium chloride sucessively, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue wasrecrystallized from a mixed solvent of ethyl acetate and hexane to givethe title compound (12.2 g) having the following physical data.

[3326] The above title compound may be prepared by the following method.2) A mixture of the compound prepared in Example 104 (1.61 g),nitrobenzene (2.46 g), ethyleneglycol (10 ml) and 10% palladium carbon(161 mg) was stirred at 200° C. for 3 hours and at 1 80“C for 17 hours.To the reaction mixture, sodium hydroxide was added at 150° C. Themixture was stirred at 180° C. for 1 hour. The reaction mixture wascooled to room temperature. Thereto were added water (10 ml) andactivated charcoal. The mixture was filtrated. The filtrate was washedby ethyl acetate (20 ml). To aqueous layer was added concentratedhydrochloric acid (2.5 ml). The mixture was extracted with ethylacetate, washed by water and a saturated aqueous solution of sodiumchloride, dried over anhydrous magnesium sulfate and concentrated. Theresidue was recrystallized from acetonitrile (25 ml) to give the titlecompound (1.46 g).

[3327] TLC: Rf 0.10 (hexane:ethyl acetate=4:1);

[3328] NMR (CDCl₃): δ 8.32 (dd, J=5.6, 1.0 Hz, 1H), 8.27 (dd, J=7.6,_(—)1.0 Hz, 1H), 8.18-8.11 (m, 1H), 7.68 (d, J=5.6 Hz, 1H), 7.51-7.41(m, 1H).

EXAMPLE 107 4-Carboxy-1,1-dioxidebenzo[b]thiophene

[3329]

[3330] To a suspension of the compound prepared in Example 106 (35 g) inmethanol (720 ml), was added a suspension of OXONE@ (362 g) in purewater (720 ml) at room temperature. The mixture was stirred at 40° C.for 2 hours. The reaction mixture was filtered. The filtrate wasconcentrated. The residue was extracted with ethyl acetate. The organiclayer was washed by a saturated aqueous solution of sodium chloride,dried over anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was crystallized from hexane, followed by dryingto give the compound of the present invention (30 g) having thefollowing physical data.

[3331] TLC: Rf 0.18 (ethyl acetate);

[3332] NMR (CDCl₃): δ 8.28 (d, J=7.5 Hz, 1H), 8.26 (d, J=7.5 Hz, 1H),7.94 (d, J=7.5 Hz, 1H), 7.66 (t, J=7.5 Hz, 1H), 6.87 (d, J=7.5 Hz, 1H).

[3333] Examples relates to different method for preparation of thecompounds of the present invention

[3334] The compounds prepared in Examples 35 (49)˜(61), Example 70,Example 94, Examples 103˜103 (29) may be prepared by the same procedureas described hereinafter in Example 108 or Example 109.

[3335] 1) For example, the compound described in Example 35 (50) may beprepared by the following procedure.

EXAMPLE 1084-(Pyridin-3-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3336]

[3337] Under an atmosphere of argon, to a solution of the compoundprepared in Example 82 in dimethylformamide (5 ml) was added a solutionof 3-(aminomethyl)pyridine (73 μl) in dimethylformamide (1 ml), followedby adding 5% palladium-carbon (50 mg). Then, an atmosphere was replacedby hydrogen. The mixture was stirred at room temperature for 1.5 hours.The reaction mixture was filtered. The filtrate was concentrated. Theobtained residue was purified with column chromatography on silica gel(chloroform methanol 25:1) followed by converting into hydrochloride byaddition of 4N hydrochloride/ethyl acetate and recrystallization usingethanol to give the compound of the present invention (231 mg).

[3338] A free compound of the compound described in Example 35 (52) maybe prepared by the following procedure.

EXAMPLE 1094-(N,N-Bis(2-hydroxyethyl)amino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3339]

[3340] To a suspension of the compound prepared in Example 82 (168 mg)in methylene chloride (2 ml) were added diethanolamine (53 μl), sodiumborocyanohydride (63 mg), concentrated hydrochloric acid (2 drops) andmethanol (0.5 ml). The mixture was stirred at room temperature for 6hours. The reaction mixture was poured into water, and extracted with amixed solvent (methylene chloride and methanol). The organic layer waswashed by a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedwith column chromatography on silica gel to give the compound of thepresent invention (50 mg).

[3341] 2) The compound prepared in Example 81 (1) may be prepared by thesame procedure as described in Example 27 using the compound prepared inExample 107 instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, and ifnecesary, by converting into a corresponding free compound by a knownmethod.

[3342] 3) The compounds prepared in Examples 35˜35 (32), Examples 45(1)˜45 (2), Example 70, Example 71 and Example 87 may be prepared by thesame procedure as described in Example 100.

[3343] For example, the compound prepared in Example 35 (11) may beprepared by the same procedure as described in Example 100 using thecompound (free compound or sodium salt) prepared in Example 81 (1), and2-(piperidin-1-yl)ethylamine instead of furan-2-ylmethylamine.

FORMULATION EXAMPLE Formulation Example 1

[3344] The following components were admixed in a conventional methodand punched out to obtain 100 tablets each containing 50 mg of activeingredient. 4-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-5.0 g dioxidebenzo[b]thiophene Carboxymethylcellulose calcium(disintegrating agent) 0.2 g Magnesium stearate (lubricating agent) 0.1g Microcrystalline cellulose 4.7 g

Formulation Example 2

[3345] The following components were admixed in a conventional method,and the solution was sterilized in a conventional method, placed 5 mlportions into ampoules and freeze-dried in a conventional method toobtain 100 ampoules each containing 20 mg of active ingredient.4-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-  2.0 gdioxidebenzo[b]thiophene Mannitol   20 g DIstilled water  500 ml

1. An inhibitor of producing interleukin-6 and/or interieukin-12comprising, as an active ingredient, a fused thiophene derivative of theformula (I)

[wherein

is a single or double bond, Y is

 or (ii) hydrogen  (with a proviso that when

is a double bond, Y is hydrogen, and when

is a single bond, Y is

m and n are each independently 0 or an integer of 1-2, p is 0 or aninteger of 1-4, q is 0 or an integer of 1-5, Z is single bond, C1-8alkylene, C2-8 alkenylene or C2-8 alkynylene,

 is (i) benzene ring or (ii) 6-membered monocyclic hetero arylcontaining 1-2 nitrogen atom(s),

 is (i) C3-15 mono-, bi- or tricyclic carbo ring or (ii) 4-18 memberedmono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2oxygen atom(s) and/or one sulfur atom, each R¹ of (R¹)p isindependently, (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl,(iv) nitro, (v) cyano, (vi) halogen, (vii) Cyc¹, (viii) C1-8 alkyl, C2-8alkenyl or C2-8 alkynyl substituted with halogen or Cyc¹ or (ix)—A¹—A²—A³, A¹ is (i) single bond, (ii) C1-8 alkylene, (iii) C2-8alkenylene or (iv) C2-8 alkynylene, A² is (i) —O—, (ii) —NR³— (iii)—C(O)—, (iv) —CH(OH)—, (v) —C(O)NR⁴—, (vi) —NR⁵C(O)—, (vii) —C(O)O—,(viii) —OC(O)—, (ix) —SO₂NR⁶—, (x) —NR⁷SO₂—, (xi) —C(O)NR⁹O—, (xii)—OC(O)NR¹⁰—, (xiii) —NR¹¹C(O)NR¹²—, (xiv) —NR¹³C(O)O— or (xv) —OC(O)O—(wherein R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹² and R¹³ are eachindependently, hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substitutedwith Cyc¹, —OR¹⁴ (wherein R¹⁴ is hydrogen or C1-8 alkyl.) or cyano, withthe proviso that the linkage of the right side of each group representedby A² binds to A³. A³ is (i) hydrogen, (ii) C1-8 alkyl, (iii) C2-8alkenyl, (iv) C2-8 alkynyl, (v) Cyc¹ or (vi) C1-8 alkyl, C2-8 alkenyl orC2-8 alkynyl substituted with 1-3 groups selected from the following(a)-(i): (a) halogen, (b) cyano, (c) —P(O)(R¹⁵)₂, (d) —Si(R¹⁶)₃, (e)Cyc¹, (f) —C(O)R¹⁷, (g) —OR¹⁸, (h) —NR¹⁹R²⁰, (i) —SR²¹; plural R¹⁵s areeach independently, hydroxy or C1-8 alkoxy, plural R¹⁶s are eachindependently C1-8 alkyl, R¹⁷ is (i) hydrogen, (ii) C1-8 alkyl, (iii)hydroxy, (iv) C1-8 alkoxy, (v) Cyc¹ or (vi) —NR²²R²³ (wherein R²² ishydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl, R²³is hydrogen, C1-8 alkyl, Cyc¹ or C1-8 alkyl substituted with Cyc¹ orNR²⁴R²⁵ (R²⁴ and R²⁵ are each independently hydrogen, C1-8 alkyl,phenyl, C1-8 alkyl substituted with phenyl.).), R¹⁸ is (i) hydrogen,(ii) C1-8 alkyl, (iii) C2-8 alkenyl, (iv) Cyc¹ or (v) C1-8 alkylsubstituted with Cyc¹, Si(R²)₃ (wherein plural R²⁶s are eachindependently C1-8 alkyl.) or —OR²⁷ (wherein R²⁷ is hydrogen, C1-8 alkylor C2-5 acyl.), R⁹ is (i) hydrogen, (ii) C₁-8 alkyl, (iii) phenyl or(iv) C1-8 alkyl substituted with phenyl, R²⁰ is (i) hydrogen, (ii) C1-8alkyl or (iii) —C(O)R²⁸ (wherein R²⁸ is C1-8 alkyl, C1-8 alkoxy, Cyc¹ orNR²⁹R³⁰ (wherein R29 and R³⁰ are each independently, hydrogen or C1-8alkyl.).), (iv) Cyc¹ or (v) C1-8 alkyl substituted with Cyc¹ or cyano,R²¹ is (i) hydrogen, (ii) C1-8 alkyl or (iii) Cyc¹, Cyc¹ is (i) C3-15mono-, bi- or tricyclic carbo ring or (ii) 4-18 membered mono-, bi- ortricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygenatom(s) and/or one sulfur atom, the said carbocyclic ring orheterocyclic ring may be substituted with one or more of (i) C1-8 alkyl,(ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano, (vi) nitro,(vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen, (x)diphenylmethyl, (xi) triphenylmethyl, (xii) Cyc², (xiii) —OR³¹, (xiv)—SR³², (xv) —NR³³R³⁴, (xvi) —SO₂NR³⁵R³⁶, (xvii) —C(O)R³⁷ or (xviii) C1-8alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with Cyc², hydroxy,halogen or —C(O)—Cyc², R³¹ and R³² are each independently, hydrogen,C1-8 alkyl or Cyc², R³³ is hydrogen or C1-8 alkyl, R³⁴ is hydrogen, C1-8alkyl or —C(O)-Cyc², R³⁵ is hydrogen or C1-8 alkyl, R³⁶ is hydrogen,C1-8 alkyl or Cyc², R³⁷ is hydrogen, C1-8 alkyl, —OR³⁸, —NR³⁹R⁴⁰, CyC²,or C1-8 alkyl substituted with Cyc² or —C(O)—Cyc², R³⁸, R³⁹ and R⁴⁰ areeach independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted withCyc², CyC² is (i) C3-15 mono-, bi- or tricyclic carbo ring or (ii) 4-18membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogenatom(s), 1-2 oxygen atom(s) and/or one sulfur atom, the said carbocyclicring or heterocyclic ring may be substituted with one or more of (i)C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano,(vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen,(x) —OR⁴¹, (xi) —SR⁴², (xii) —NR⁴³R⁴⁴, (xiii) —SO₂NR⁴⁵R⁴⁴, (xiv)—C(O)R⁴⁷, (xv) C₁-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted withhydroxy or halogen or (xvi) phenyl, R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵ and R⁴⁶ areeach independently, hydrogen or C1-8 alkyl, R⁴⁷ is hydrogen, C1-8 alkylor C1-8 alkoxy each R² of (R²)q is independently, (i) C1-8 alkyl, (ii)C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) —OR⁴⁸, (v) —NR⁴⁹R⁵⁰, (vi)—C(O)R⁵¹, (vii) nitro, (viii) cyano, (ix) halogen or (x) C1-8 alkyl,C2-8 alkenyl or C2-8 alkynyl substituted with —OR , —NR⁴⁹R⁵⁰, —C(O)R⁵¹,halogen or Cyc³, R⁴⁸ is (i) hydrogen, (ii) C1-8 alkyl, (iii) C2-8alkenyl, (iv) C2-8 alkynyl, (v) Cyc³ or (vi) C1-8 alkyl, C2-8 alkenyl orC2-8 alkynyl substituted with halogen, —OR⁵², —NR₅₃R⁵⁴, —C(O)R⁵⁵ orCyc³, R⁴⁹ and R⁵⁰ are each independently, hydrogen, C1-8 alkyl or—COR⁵⁹, R⁵¹ is hydrogen, C1-8 alkyl, hydroxy, C1-8 alkoxy or —NR⁶⁰R⁶¹,R⁵² is hydrogen, C1-8 alkyl, Cyc³, or C1-8 alkyl substituted with Cyc³,R⁵³ and R⁵⁴ are each independently, hydrogen, C1-8 alkyl, C2-8 alkenyl,C2-8 alkynyl or —C(O)R⁵⁶ (wherein R⁵⁶ is C1-8 alkyl, C1-8 alkoxy, Cyc³,or C1-8 alkyl substituted with Cyc³, R⁵⁵ is hydroxy, C1-8 alkoxy, or—NR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵⁸ are each independently, hydrogen, C1-8alkyl, or C1-8 alkyl substituted with Cyc³, R⁵⁹ is C1-8 alkyl or C1-8alkoxy, R⁶⁰ and R⁶¹ are each independently, hydrogen or C1-8 alkyl,Cyc³is (i) C3-15 mono-, bi- or tricyclic carbo ring or (ii) 4-18membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogenatom(s), 1-2 oxygen atom(s) and/or one sulfur atom, the said carbocyclicring or heterocyclic ring may be substituted with one or more of (i)C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) halogen, (v) cyano, (vi)hydroxy, (vii) benzyloxy, (viii) —NR⁶²R⁶³, (ix) —COOR⁶⁴, (x)trihalomethyl, (xi) trihalomethoxy, (xii) phenyl, (xiii) phenoxy, (xiv)phenylthio, (xv) C1-8 alkyl or C1-8 alkoxy substituted with phenyl,phenoxy, phenylthio, hydroxy, —NR⁶²R⁶³ or —COOR⁶⁴, R⁶² and R⁶³ are eachindependently, hydrogen or C1-8 alkyl, R⁶⁴ is hydrogen or C1-8 alkyl,with the proviso that when A² is (vi) —NR⁵C(O)—, (x) —NR⁷SO₂—, (xiv)—NR¹³C(O)O— or (xv) —OC(O)O—, then A³ is not hydrogen.], an N-oxidederivative thereof or a non-toxic salt thereof.
 2. An agent for theprevention and/or treatment of various inflammatory diseases, sepsis,multiple myeloma, plasma cell leukemia, osteoporosis, cachexia,psoriasis, nephritis, renal cell carcinoma, Kaposi's sarcoma, rheumatoidarthritis, gammopathy, Castleman's disease, atrial myxoma, diabetesmellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis,graft versus host immune diseases, infectious diseases containing afused thiophene derivative of the formula (I) depicted in claim 1, anN-oxide derivative thereof or a non-toxic salt thereof as an activeingredient.
 3. An inhibitor of producing interleukin-6 and/orinterleukin-12 according to claim 1, comprising a compound which is (1)3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (2)6-nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(3) 3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(4) 4,5-dimethyl-1,1-dioxidebenzo[b]thiophene, (5)4,6-dimethyl-1,1-dioxidebenzo[b]thiophene, (6)4,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (7)5,6-dimethyl-1,1-dioxidebenzo[b]thiophene, (8)5,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (9)6,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (10)4-carboxymethyl-1,1-dioxidebenzo[b]thiophene, (11)6-(2,2-bis(ethoxycarbonyl)ethenyl)amino-1,1-dioxidebenzo[b]thiophene,(12) 4-methylaminocarbonyloxy-1,1-dioxidebenzo[b]thiophene, (13)5-(2-(N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino)ethyl)-1-dioxidebenzo[b]thiophene, (14)5-(2-hydroxyethyl)-1,1-dioxidebenzo[b]thiopherie, (15)5-bromo-7-methyl-1,1-dioxidebenzo[b]thiophene, (16) 7-bromo-5-methyl-methyl-1,1-dioxidebenzo[b]thiophene, (17)5-bromo-6-methyl-1,1-dioxidebenzo[b]thiophene, (18)5-bromo-4-methyl-1,1-dioxidebenzo[b]thiophene, (19)6-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene, (20) 4-bromo-5-methyl--methyl-1,1-dioxidebenzo[b]thiophene, (21)6-amino-1,1-dioxidebenzo[b]thiophene, (22)6-acetylamino-1,1-dioxidebenzo[b]thiophene, (23)6-(4-diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene, (24)1,1-dioxidethieno[2,3-b]pyridine, (25) 1,1-dioxidethieno[3,2-b]pyridine,(26) 1,1-dioxidethieno[2,3-c]pyridine, (27)5-amino-1,1-dioxidebenzo[b]thiophene, (28)5-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene,(29)4-(2-(1,1-dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene,(30) 7-methyl-1,1-dioxidethieno[2,3-c]pyridine, (31)1,1-dioxidebenzo[b]thiophene, (32)4-(4-methoxyphenyl)-1,1-dioxidethieno[3,2-c]pyridine, (33)5-((E)-2-(ethoxycarbonyl)ethenyl)-4-methoxybenzo[b]thiophene, (34)5-(2-(ethoxycarbonyl)ethyl-4-methoxybenzo[b]thiophene, (35)5-methoxycarbonyl-4-ethoxybenzo[b]thiophene, (36)5-carboxy-4-ethoxybenzo[b]thiophene, (37)5-benzyloxycarbonyl-4-ethoxybenzo[b]thiophene, (38)5-hydroxy-4-formylbenzo[b]thiophene, (39)5-benzyloxy-4-formylbenzo[b]thiophene, (40)5-benzyloxy-4-hydroxymethylbenzo[b]thiophene or (41)4-t-butoxycarbonylaminobenzo[b]thiophene, or an N-oxide derivativethereof, or a non-toxic salt thereof as active ingredient.
 4. A fusedthiophene derivative of formula (IA)

[wherein

is a single or double bond, Y is (i)

 or (ii) hydrogen  (with a proviso that when

is a double bond, Y is hydrogen, and when

is a single bond, Y is

m and n are each independently 0 or an integer of 1-2, p is 0 or aninteger of 1-4, q is 0 or an integer of 1-5, Z is single bond, C1-8alkylene, C2-8 alkenylene or C2-8 alkynylene,

is (i) benzene ring or (ii) 6-membered monocyclic hetero aryl containing1-2 nitrogen atom(s),

 is (i) C3-15 mono-, bi- or tricyclic carbo ring or (ii) 4-18 memberedmono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2oxygen atom(s) and/or one sulfur atom, each R¹ of (R¹)p isindependently, (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl,(iv) nitro, (v) cyano, (vi) halogen, (vii) Cyc¹, (viii) C1-8 alkyl, C2-8alkenyl or C2-8 alkynyl substituted with halogen or Cyc¹ or (ix)—A¹—A²—A³, A¹ is (i) single bond, (ii) C1-8 alkylene, (iii) C2-8alkenylene or (iv) C2-8 alkynylene, A² is (i) —O—, (ii) —NR³— (iii)—C(O)—, (iv) —CH(OH)—, (v) —C(O)NR⁴—, (vi) —NR⁵C(O)—, (vii) —C(O)O—,(viii) —OC(O)—, (ix) —SO₂NR⁶—, (x) —NR⁷SO₂—, (xi) —C(O)NR⁹O—, (xii)—OC(O)NR¹⁰, (xiii) —NR¹¹C(O)NR¹²—, (xiv) —NR¹³C(O)O— or (xv) —OC(O)O—(wherein R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹² and R¹³ are eachindependently, hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substitutedwith Cyc¹, —OR⁴ (wherein R¹⁴ is hydrogen or C1-8 alkyl.) or cyano, withthe proviso that the linkage of the right side of each group representedby A² binds to A³. A³ is (i) hydrogen, (ii) C1-8 alkyl, (iii) C2-8alkenyl, (iv) C2-8 alkynyl, (v) Cyc¹ or (vi) C1-8 alkyl, C2-8 alkenyl orC2-8 alkynyl substituted with 1-3 groups selected from the following(a)-(i): (a) halogen, (b) cyano, (c) —P(O)(R¹⁵)₂, (d) —Si(R¹⁶)₃, (e)Cyc¹, (f) —C(O)R¹⁷, (g) —OR¹⁸, (h) —NR¹⁹R²⁰, (i) —SR²¹; plural R¹⁵s areeach independently, hydroxy or C1-8 alkoxy, plural R¹⁶s are eachindependently C1-8 alkyl, R¹⁷ is (i) hydrogen, (ii) C1-8 alkyl, (iii)hydroxy, (iv) C1-8 alkoxy, (v) Cyc¹ or (vi) —NR²²R²³ (wherein R²² ishydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl, R²²is hydrogen, C1-8 alkyl, Cyc¹ or C1-8 alkyl substituted with Cyc¹ orNR²⁴R²⁵ (R²⁴ and R25 are each independently hydrogen, C1-8 alkyl,phenyl, C1-8 alkyl substituted with phenyl.).), R¹⁸ is (i) hydrogen,(ii) C1-8 alkyl, (iii) C2-8 alkenyl, (iv) Cyc¹ or (v) C1-8 alkylsubstituted with Cyc¹, Si(R²⁶)₃ (wherein plural R²⁶s are eachindependently C1-8 alkyl.) or —OR²⁷ (wherein R²⁷ is hydrogen, C1-8 alkylor C2-5 acyl.), R¹⁹ is (i) hydrogen, (ii) C1-8 alkyl, (iii) phenyl or(iv) C1-8 alkyl substituted with phenyl, R²⁰ is (i) hydrogen, (ii) C1-8alkyl or (iii) —C(O)R²⁸ (wherein R²⁸ is C1-8 alkyl, C1-8 alkoxy, Cyc¹ orNR²⁹R³⁰ (wherein R²⁹ and R³⁰ are each independently, hydrogen or C1-8alkyl.).), (iv) Cyc¹ or (v) C1-8 alkyl substituted with Cyc¹ or cyano,R21 is (i) hydrogen, (ii) C1-8 alkyl or (iii) Cyc¹, Cyc¹ is (i) C3-15mono-, bi- or tricyclic carbo ring or (ii) 4-18 membered mono-, bi- ortricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygenatom(s) and/or one sulfur atom, the said carbocyclic ring orheterocyclic ring may be substituted with one or more of (i) C1-8 alkyl,(ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano, (vi) nitro,(vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen, (x)diphenylmethyl, (xi) triphenylmethyl, (xii) Cyc², (xiii) —OR³, (xiv)—SR³², (xv) —NR³³R³⁴, (xvi) —SO₂NR³⁵R³⁶, (xvii) —C(O)R³⁷ or (xviii) C1-8alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with Cyc², hydroxy,halogen or —C(O)—Cyc², R³¹ and R³² are each independently, hydrogen,C1-8 alkyl or Cyc², R³³ is hydrogen or C1-8 alkyl, R³⁴ is hydrogen, C1-8alkyl or —C(O)-Cyc², R³⁵ is hydrogen or C1-8 alkyl, R³⁶ is hydrogen,C1-8 alkyl or Cyc², R³⁷ is hydrogen, C1-8 alkyl, —OR³, —NR³⁹R⁴⁰, Cyc²,or C1-8 alkyl substituted with Cyc² or —C(O)-Cyc², R³⁸, R³⁹ and R⁴⁰ areeach independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted withCyc², Cyc² is (i) C3-15 mono-, bi- or tricyclic carbo ring or (ii) 4-18membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogenatom(s), 1-2 oxygen atom(s) and/or one sulfur atom, the said carbocyclicring or heterocyclic ring may be substituted with one or more of (i)C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano,(vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen,(x) —OR⁴ , (xi) —SR⁴², (xii) —NR⁴R⁴⁴, (xiii) —SO₂NR⁴⁵R⁴⁶, (xiv)—C(O)R⁴⁷, (xv) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted withhydroxy or halogen or (xvi) phenyl, R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵ and R⁴⁶ areeach independently, hydrogen or C1-8 alkyl, R⁴⁷ is hydrogen, C1-8 alkylor C1-8 alkoxy each R² of (R²)q is independently, (i) C1-8 alkyl, (ii)C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) —OR⁴⁸, (v) —NR⁴⁹R⁵⁰, (vi)—C(O)R⁵¹, (vii) nitro, (viii) cyano, (ix) halogen or (x) C1-8 alkyl,C2-8 alkenyl or C2-8 alkynyl substituted with —OR⁴⁸, —NR⁴⁹R⁵⁰, —C(O)R⁵¹,halogen or Cyc³, R⁴⁸ is (i) hydrogen, (ii) C1-8 alkyl, (iii) C2-8alkenyl, (iv) C2-8 alkynyl, (v) Cyc³ or (vi) C1-8 alkyl, C2-8 alkenyl orC2-8 alkynyl substituted with halogen, —OR⁵², —NR⁵³R⁵⁴, —C(O)R⁵⁵ orCyC³, R⁴⁹ and R⁵⁰ are each independently, hydrogen, C1-8 alkyl or—COR⁵⁹, R⁵¹ is hydrogen, C1-8 alkyl, hydroxy, C1-8 alkoxy or —NR⁶⁰R⁶¹,R52 is hydrogen, C1-8 alkyl, Cyc³, or C1-8 alkyl substituted with Cyc³,R⁵³ and R⁵⁴ are each independently, hydrogen, C1-8 alkyl, C2-8 alkenyl,C2-8 alkynyl or —C(O)R⁵⁶ (wherein R⁵⁶ is C1-8 alkyl, C1-8 alkoxy, Cyc³,or C1-8 alkyl substituted with Cyc³), R⁵⁹ is hydroxy, C1-8 alkoxy, or—NR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵⁸ are each independently, hydrogen, C1-8alkyl, or C1-8 alkyl substituted with Cyc³), R⁵⁹ is C1-8 alkyl or C1-8alkoxy, R⁶⁰ and R⁶¹ are each independently, hydrogen or C1-8 alkyl, Cyc³is (i) C3-15 mono-, bi- or tricyclic carbo ring or (ii) 4-18 memberedmono-, bi- or tricyclic hetero ring containing 14 nitrogen atom(s), 1-2oxygen atom(s) and/or one sulfur atom, the said carbocyclic ring orheterocyclic ring may be substituted with one or more of (i) C1-8 alkyl,(ii) C1-8 alkoxy, (iii) nitro, (iv) halogen, (v) cyano, (vi) hydroxy,(vii) benzyloxy, (viii) —NR⁶²R⁶ , (ix) —COOR⁶⁴, (x) trihalomethyl, (xi)trihalomethoxy, (xii) phenyl, (xiii) phenoxy, (xiv) phenylthio, (xv)C1-8 alkyl or C1-8 alkoxy substituted with phenyl, phenoxy, phenylthio,hydroxy, —NR⁶²R⁶³ or —COOR⁶⁴, R⁶² and R⁶³ are each independently,hydrogen or C1-8 alkyl, R⁶⁴ is hydrogen or C1-8 alkyl, with the provisothat when (1) when A² is (vi) —NR⁵C(O)—, (x) —NR⁷SO₂—, (xiv) —NR¹³C(O)O—or (xv) —OC(O)O—, then A³ is not hydrogen, (2) when

is a double bond and Y is hydrogen, then n is 1 or 2, (3) when

is a single bond, Y is

 n is 2, m is 0 or 2, p is 0 or an integer of 1-4, ring A and ring B arebenzene ring, R¹ is C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro orC1-8 alkyl substituted with halogen, then q is not 0, (4) when

is a single bond, Y is

 n is 2, m is 0 or 2, p is 0 or an integer of 1-4, ring A and ring B arebenzene ring, R¹ is C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro orC1-8 alkyl substituted with halogen, and q is an integer of 1-5, then R²is not C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro or C1-8 alkylsubstituted with halogen, (5) when

is a double bond, Y is hydrogen, n is 2, p is 1 and ring A is benzenering, then R¹ is not halogen, C1-8 alkyl, phenylsulfonylamino,2-methylphenylsulfonylamino, 3-methylphenylsulfonylamino,4-methylphenylsulfonylamino, hydroxy, C1-8 alkoxy, nitro, or C1-8 alkoxysubstituted with carboxy, hydroxy, C1-8 alkoxycarbonyl orhydroxyaminocarbonyl, (6) when

is a double bond, Y is hydrogen, n is 2, p is 2 and ring A is benzenering and one R¹ is phenylsulfonylamino, 2-methylphenylsulfonylamino,3-methylphenylsulfonylamino or 4-methylphenylsulfonylamino, then theother R¹ is not C1-8 alkyl, (7) when

is a double bond, Y is hydrogen, n is 2, p is 2-3, ring A is benzenering, one R¹ is hydroxy, C1-8 alkoxy, or C1-8 alkoxy substituted withcarboxy, hydroxy, C1-8 alkoxycarbonyl or hydroxyaminocarbonyl, then theother R¹ is neither halogen nor C1-8 alkyl, (8) when

is a double bond, Y is hydrogen, n is 2, p is 3-4 and ring A is benzenering, then two or three R¹ are not t-butyl at the same time, and (9) thefollowing compounds (1)-(32) are excluded: (1)3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (2)6-nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(3) 3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(4) 4,5-dimethyl-1,1-dioxidebenzo[b]thiophene, (5)4,6-dimethyl-1,1-dioxidebenzo[b]thiophene, (6)4,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (7)5,6-dimethyl-1,1-dioxidebenzo[b]thiophene, (8)5,7-dimethyl-1,1-dioxidebenzo[b[thiophene, (9)6,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (10)4-carboxymethyl-1,1-dioxidebenzo[b]thiophene, (11)6-(2,2-bis(ethoxycarbonyl)ethenyl)amino-1,1-ioxidebenzo[b]thiophene,(12) 4-methylaminocarbonyloxy-1,1-dioxidebenzo[b]thiophene, (13)5-(2-(N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino)ethyl)-1,1-dioxidebenzo[bjthiophene,(14) 5-(2-hydroxyethyl)-1,1-di oxidebenzo[b]thiophene, (15)5-bromo-7-methyl-1,1-dioxidebenzo[b]thiophene, (16)7-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene, (17)5-bromo-6-methyl-1,1-dioxidebenzo[b]thiophene, (18)5-bromo-4-methyl-1,1-dioxidebenzo[b]thiophene, (19)6-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene, (20)4-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene, (21)6-amino-1,1-dioxidebenzo[b]thiophene, (22)6-acetylamino-1,1-dioxidebenzo[b]thiophene, (23)6-(4-diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene, (24)1,1-dioxidethieno[2,3-b]pyridine, (25) 1,1-dioxidethieno[3,2-b]pyridine,(26) 1,1-dioxidethieno[2,3-c]pyridine, (27)5-amino-1,1-dioxidebenzo[b]thiophene, (28)5-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene,(29)4-(2-(1,1-dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene,(30) 7-methyl-1,1-dioxidethieno[2,3-c]pyridine, (31)1,1-dioxidebenzo[b]thiophene or (32)4-(4-methoxyphenyl)-1,1-dioxidethieno[3,2-c]pyridine.], an N-oxidederivative thereof or a non-toxic salt thereof.
 5. A fused thiophenederivative of the formula (IA) depicted in claim 4, wherein

is a double bond, an N-oxide derivative thereof, or a non-toxic saltthereof.
 6. A fused thiophene derivative of the formula (IA) depicted inclaim 4, wherein

is a single bond, an N-oxide derivative thereof or a non-toxic saltthereof.
 7. A fused thiophene derivative of the formula (IA) depicted inclaim 4, wherein

is benzene, an N-oxide derivative thereof or a non-toxic salt thereof.8. A fused thiophene derivative of the formula (IA) depicted in claim 4,wherein

is 6-membered monocyclic hetero aryl containing 1-2 nitrogen atom(s), anN-oxide derivative thereof or a non-toxic salt thereof.
 9. A fusedthiophene derivative of the formula (IA) depicted in claim 4, wherein

is a C3-15 mono-, bi- or tricyclic carbo ring, an N-oxide derivativethereof, or a non-toxic salt thereof.
 10. A fused thiophene derivativeof the formula (IA) depicted in claim 4, wherein

is a 4-membered mono-, bi- or tricyclic hetero ring containing 1-4nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, an N-oxidederivative thereof, or a non-toxic salt thereof.
 11. A fused thiophenederivative of the formula (IA) depicted in claim 4, wherein

is 5-10 membered mono-, bi- or tricyclic hetero ring containing 1-4nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, an N-oxidederivative thereof, or a non-toxic salt thereof.
 12. A fused thiophenederivative of the formula (IA) depicted in claim 4, wherein

is 11-18 membered mono-, bi- or tricyclic hetero ring containing 1-4nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, an N-oxidederivative thereof, or a non-toxic salt thereof.
 13. A compoundaccording to claim 4, which is (1)3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (2)3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (3)3-(4-methylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (4)3-(4-methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (5)3-(4-chlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (6)3-(4-fluorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (7)3-(4-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (8)3-(3-hydroxyphenyl)thio-2,3-dihydro-_(1,1)-dioxidebenzo[b]thiophene, (9)3-(2-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (10)3-(pyridin-4-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (11)3-(pyrimidin-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (12)3-(thiazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (13)3-(3-methylfuran-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(14) 3-(3-methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(15)3-(2-methoxycarbonylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(16) 3-cyclohexylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (17)3-(naphthalen-1-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (18)3-(2-methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (19)3-(1-methylimidazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(20) 3-phenylsulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (21)3-(thiophen-2-yl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (22)3-(2-methoxycarbonylphenyl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(23) 3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (24)3-(thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(25) 3-(4-methylphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (26)3-(4-methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(27)3-(4-chlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(28)3-(4-fluorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(29)3-(4-hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(30)3-(3-hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dloxidebenZo[b]thiophene,(31)3-(2-hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(32) 3-(pyridin-4-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(33)3-(pyrimidin-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(34) 3-(thiazol-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(35)3-(3-methylfuran-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(36)3-(3-methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(37) 3-(2-methoxycarbonylphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (38)3-cyclohexylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (39)3-(naphthalen-1-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(40)3-(2-methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(41)3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(42)3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(43) 3-(4-(2-(morpholin-4-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (44)3-(3-benzyloxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(45)3-(2-benzyloxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(46) 3-(4-(pyridin-2-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (47)3-(4-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (48)3-(4-pyridin-4-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(49) 3-(4-(3-hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (50)3-(3-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(51)3-(3-(3-hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(52)3-(2-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(53)3-(2-(3-hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(54)3-(4-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(55)3-(3-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(56) 3-(4-(pyridin-2-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (57)3-(4-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(58) 3-(4-(pyridin-4-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (59)3-(4-(3-hydroxypropyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(60)3-(3-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(61) 3-(3-(3-hydroxypropyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (62)3-(2-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(63) 3-(2-(3-hydroxypropyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (64)3-(4-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(65)3-(3-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(66)3-(4-(2-aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(67)3-(3-(2-aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[bjthiophene,(68)3-(4-(2-(N,N-dimethylamino)ethyloxyphenyl)sulfonyl-2,3dihydro-1,1-dioxidebenzo[b]thiophene,(69)3-(3-(2-(N,N-dimethylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(70) 5-nitro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (71)6-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (72)4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (73)5-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (74)7-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (75)4-chloro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (76)5-(t-butoxycarbonylamino)methyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (77)4,7-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (78)4,6-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (79)4-ethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (80)4-methoxy-5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(81) 4-bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (82)4-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (83)5-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (84)6-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (85)7-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (86)3-phenylthio-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine, (87)4,7-dihydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(88) 5-nitro-3-phenyisulfonyl-2,3-dihydro-1,1-di oxidebenzo[b]thiophene,(89)6-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(90)4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(91)5-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(92)7-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(93) 4-chloro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(94) 4-(t-butoxycarbonylamino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (95)4,7-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(96)4,6-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(97) 4-ethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(98)4-methoxy-5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(99) 4-bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(100)4-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(101)5-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene(102)6-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(103)7-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(104) 3-phenylsulfonyl-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine,(105) 5-amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(106)5-acetylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(107)4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(108) 4-(N,N-dimethylamino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (109)4-methoxy-5-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(110)4-methoxy-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(111 )4-methoxy-3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(112)4-(4-nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(113) 4-(3-phenyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (114)4-benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (115)4-(3-benzyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(116)4-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(117)4-(quinolin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(118)4-(pyridin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(119)4-(pyridin-4-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(120)4-(3-(pyridin-3-yl)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(121)4-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(122) 5-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(123)5-(2-phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(124)5-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(125)5-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(126) 5-(3-(pyridin-3-yl) propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (127)6-(3-phenyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (128)6-benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (129)6-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (130)6-(2-(morpholin-4-yl) ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (131)6-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(132) 6-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (133)6-(3-nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(134)6-(3-bromopropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(135) 7-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(136)7-(2-phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(137)7-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(138)7-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(139)4-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(140)5-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(141)6-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(142)7-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(143)4-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(144)4-(3-(t-butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(145) 5-(2-(t-butoxycarbonylamino) ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[bjthiophene, (146)6-(3-(t-butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(147)6-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(148) 7-(2-(t-butoxycarbonylamino) ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (149)4-(N-(t-butoxycarbonyl)piperidin-4-yl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(150)4,7-bis[(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(151)4-(3-nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(152)4,7-bis(pyridin-3-ylmethyloxy)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(153)4-(3-hydroxypropyl)oxy-3-phenylsulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(154)4-(4-nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(155)4-(3-phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(156)4-benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(157)4-(3-benzyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(158) 4-(pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (159)4-(N-oxidequinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(160)4-(pyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(161)4-(N-oxidepyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(162)4-(pyridin-4-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(163) 4-(3-(pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(164)4-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(165)5-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(166) 5-(2-phenyloxyethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (167)5-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(168) 5-(pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (169)5-(3-(pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(170)6-(3-phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(171)6-benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(172)6-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(173)6-(2-(morpholin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(174)6-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(175)6-(pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(176)6-(3-nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(177)6-(3-bromopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(178)7-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(179)7-(2-phenyloxyethyl)oxy-3-phenylsuffonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(180) 7-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (181)7-(pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(182) 7-(N-oxidepyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (183)4-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(184)5-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(185)6-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(186)7-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(187)4-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(188) 4-(3-(t-butoxycarbonylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(189)5-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(190) 6-(3-(t-butoxycarbonylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(191)6-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(192)7-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(193) 4-(N-(t-butoxycarbonyl)piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(194)4,7-bis[(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(195)4-(3-nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(196)4-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(197)5-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(198)6-carboxymethoxy-3-phenylsutfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(199)7-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(200) 4-(N-(pyridin-3-ylmethyl)carbamoylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (201)4-((2-(N,N-dimethylamino)ethylamino)carbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(202)4-(N-benzyl-2-(N′,N′-dimethylamino)ethylamino)carbonymethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(203)4-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(204)4-(3-aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(205)5-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(206)6-(3-aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(207)6-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(208)7-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(209)4-(piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(210) 4,7-bis[(2-aminoethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (211)4-(2-(N,N-dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(212) 4-(3-(N,N-dimethylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (213)4-(3-(N-cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(214)5-(2-(N,N-dimethylamino)ethyl)oxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(215)6-(3-(N,N-dimethylamino)propyl)oxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(216)6-(3-(N-cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(217)6-(2-(N,N-dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(218)7-(2-(N,N-dimethylaminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(219)4-(3-aminophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(220)4-(3-(pyridin-3-ylcarbonylamino)phenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(221)4-(2-(pyridin-3-ylcarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(222)5-methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(223)5-(4-chlorophenylcarbonyl)amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(224) 4-cyano-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(225) 6-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(226)4,7-dimethoxy-3-phenylsulfonyl-2;3-dihydro-1,1-dioxidebenzo[b]thiophene,(227)4,7-bis(3-hydroxypropyl)oxy-3-phenyIsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(228) 4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(229)4-(4-benzylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(230) 4-(N-(2-(pyridin-3-yl)ethyl)-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(231) 4-(2-(2-hydroxyethoxy)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(232) 4-(2,4-dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(233) 4-(1-benzylpiperidin-4-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(234) 4-(pyridin-4-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(235) 4-(2-t-butoxycarbonylethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(236)4-(thiophen-2-ylmethyl)carbamoyl-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(237)4-benzylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(238)4-(pyridin-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(239)4-(2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(240)4-((1S)-1-t-butoxycarbonyl-2-methylpropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(241)4-(2-fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(242)4-(3-fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(243)4-(3-methylphenylmethyl)carbamoyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(244)4-(2-methoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(245)4-(2,3-dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(246)4-(3,4-dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(247)4-(2,5-difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(248)4-(3,4,5-trimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(249) 4-(benzimidazol-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(250) 4-(3,5-difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(251)4-(N-benzyl-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(252)4-(4-nitrophenymethyl)carbamoyl-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(253)5-(2-hydroxyethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(254)5-(pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(255)5-(2-dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(256)5-dimethylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(257)5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(258)5-(2,3-dihydroindol-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(259)5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(260) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(261)4-(pyridin-3-ylcarbonyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(262) 4-(3-(pyrrol-1-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(263)4-(quinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(264)4-(2-(pyrrol-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(265) 4-(2-(4-methylthiazol-5-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (266)4-(3-(pyridin-4-yl)propyl)oxy-3-phenylsuffonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(267)4-(1-t-butoxycarbonylpiperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(268)4-(2-(pyrrolidin-1-yl)ethyl)oxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(269)4-(2-(piperidin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(270)4-(2-(2-acetyloxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(271)4-(2-(4-benzylpiperazin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(272)4-diethylcarbamoylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(273) 4-cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (274)5-(pyridin-3-yloxy)methyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(275)5-(2-(t-butoxycarbonylamino)ethyl)oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(276) 5-((2E)-3-ethoxycarbonyl-2-propenyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (277)4-(2,4-dimethoxyphenylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (278) 4-(pyridin-3-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(279)4-(2-dimethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(280)4-(N,N-bis(2-hydroxyethyl)amino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(281)4-(2-(2-hydroxyethoky)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(282) 4-(4-benzylpiperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (283)4-(4-(pyridin-2-yl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(284)4-(4-ethoxycarbonylpiperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(285) 4-(4-(2-hydroxyethyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (286)4-(4-(pyridin-4-yl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(287)4-benzylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(288)4-(1-benzylpiperidin-4-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(289)4-(morpholin-4-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(290)4-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(291)4-benzyloxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(292)4-(pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(293)6-(pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(294)4-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(295) 6-bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(296) 6-amino-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(297)5-methyicarbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(298)4-dimethylxarbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(299) 4-carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(300)4-(2-(pyridin-4-yl)ethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(301)4-(2-(pyridin-3-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(302)4-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(303)6-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(304)6-cyanomethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(305)5-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(306)7-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(307)5-benzyloxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(308)5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(309)7-methoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(310)7-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(311)5-t-butoxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(312)5-(2-(ethoxycarbonyl)ethyl)-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(313)4-(furan-2-ylmethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(314) 5-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (315)3-benzylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (316)3-(3,4-dichlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(317) 3-(4-nitrophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(318)5-hydroxymethyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(319)4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(320) 6-fl uoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(321) 4-fluoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(322)5-methylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(323)4-dimethylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(324)4-carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(325)4-(2-(pyridin-4-yl)ethyl)oxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(326)4-(2-(pyridin-3-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(327)4-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(328)6-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(329)6-cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(330)5-ethoxycarbonylmethyloxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(331)7-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(332)5-benzyloxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(333)5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(334)7-methoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(335)7-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(336)5-t-butoxycarbonyl-4-methoxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(337)5-(2-ethoxycarbonylethyl)-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(338) 3-benzylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (339)3-(3,4-dichlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(340)3-(4-nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(341)5-hydroxymethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(342)4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(343)6-fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(344)4-fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(345)5-benzylozycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(346)5-benzyloxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(347)5-benzyloxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(348)5-benzyloxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(349)5-carboxy-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(350)5-carboxy-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(351)5-carboxy-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(352)5-carboxy-4-octyloxy-3-phenylsuldonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(353)5-methoxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(354)5-methoxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(355)5-methoxycarbonyl-4butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(356)5-methoxycarbonyl-4-octyloxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(357)5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(358)5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(359)5-(dimethylaminoethylcarbamoyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (360)5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(361)5-(2,3-dihydroindol-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(362)5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(363)5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (364)5-(2-dimethylaminoethyl)carbamoyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (365)5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(366)5-(2,3-dihydroindol-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (367)5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(368) 5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(369)5-(2-dimethylaminoethyl)carbamoyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(370)5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(371) 5-(2,3-dihydroindol-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(372)5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(373) 5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(374)5-(2-dimethylaminoethyl)carbamoyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(375)5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(376)5-(2,3-dihydroindol-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (377)5-benzyloxy-4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(378)5-benzyloxy-4-bromomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(379)5-benzyloxy-4-aminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(380)5-benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(381)5-benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(382)5-benzyloxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(383)5-hydroxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(384)5-methoxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(385) 5-(3-phenylpropyl)oxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(386)5-methoxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(387)5-(3-phenylpropyl)oxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(388)5-benzyloxy-4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(389)5-benzyloxy-4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(390)5-benzyloxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(391)5-hydroxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsuifonyi-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(392)4,7-dimethoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(393) 6-bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(394)4-(piperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(395)5-(2-aminoethyl)oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(396)4-(2-(2-hydroxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(397)5-carboxy-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(398)4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(399)4-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(400)5-(4-phenylbutyl)aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(401)5-(pyridin-3-ylmethyl)aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(402)6-dimethylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(403)4-(2-dimethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(404)4,7-bis(pyridin-3-ylmethyloxy)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(405) 4-(N-oxidepyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (406)4-(2-(N-oxidepyridin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (407)4-methoxy-3-(4-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(408)4-methoxy-3-(4-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(409) 4-methoxy-3-(4-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (410)5-(2-dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(411)5-(pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(412)4-(2-(piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(413)4-(furan-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(414)4-(2,4,6-trimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(415)4-(3-(2-oxopyrrolidin-1-yl)propyl)carbamoyl-3-phenylsuIfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(416)4-((3S)-1-benzylpyrrolidin-3-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(417)4-(2-(pyrrolidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(418) 4-(2-diethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(419)4-(2-(N-ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(420)4-(N-ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(421) 4-(3-(imidazol-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(422)4-((3R)-1-benzylpyrrolidin-3-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(423)4-(3-(pyrrolidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(424)4-(N-2-(piperidin-1-yl)ethyl-N-methyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(425)4-(3,5-dimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(426)4-(3-(piperidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(427)4-(2-diisopropylamino)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(428)4-(2-(morpholin-4-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(429)4-(N-2-(piperidin-1-yl)ethyl-N-propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(430) 4-(N-2-(piperidin-1-yl)ethyl-N-isopropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(431)4-(4-benzoylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(432)4-(4-(4-ethylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(433)4-(4-(4-phenylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(434) 4-(4-(1,3-dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(435) 4-(4-benzyloxycarbonylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(436) 4-(4-(2-methylphenyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(437) 4-(4-(4-methoxyphenyl) piperazin-1-yl)carbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (438)4-(2-(pyridin-2-yl)ethyl) oxy-3-phenylthio-1,1-dioxidebenzo[b]thiophene,(439)4-(2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(440)4-(2-(piperidin-1-yl)ethyl)carbamoyl-3-(4-nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(441)4-(N-2-(piperidin-1-yl)ethyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(442)4-(2-(N-ethyl-N-3-methylphenyl)aminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(443)4-(N-benzyl-N-ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(444)4-(2-diethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(445)4-(4-methylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(446)4-(N-ethyl-N-2-(piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(447) 4-(2-methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(448)4-(3-phenylpropyi)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(449)4-(3,5-dimethoxybenzyl)aminomethyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(450)4-((3R)-1-benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(451)4-((3S)-1-benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(452)4-(2-phenylethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(453)4-(N-benzyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(454)4-(3-(2-oxopyrrolidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(455)4-(4-aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(456) 4-(4-((2E)-3-phenyl-2-propenyl) piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (457)4-(2-aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(458)4-(4-benzylpiperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(459)4-(4-chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(460)4-(3-chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(461)4-(3-methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(462)4-(3,4-dichlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(463)4-(1,3-dioxaindan-5-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(464)4-(2,3-dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(465)4-(3,4,5-trimethoxybenzyl)aminomethyl3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(466) 4-(4-(t-butyloxycarbonyl) piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (467)4-(2-diisopropylamino) ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(468) 4-(2-(morpholin-4-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(469) 4-(N-2-(piperidin-1-yl)ethyl-N-propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(470)4-(N-2-(piperidin-1-yl)ethyl-N-isopropyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(471) 4-(3,4-dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(472)4-(3-(2-methylpiperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(473) 4-(4-(piperidin-1-yl)piperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (474)4-(3-(piperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(475)4-(3-bromobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(476)4-(4-nitrobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(477)4-(4-aminosulfonylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(478)4-(piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(479) 4-(2,4,6-trimethoxybenzyl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (480)4-(piperidin-1-yl)carbonylmethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(481)4-(pyrrolidin-1-yl)ethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,(482) 4-(4-(1,3-dioxaindan-5-ylmethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, or an N-oxide derivative thereof ora non-toxic salt thereof.
 14. A compound ccording to claim 4, which is(1) 4-(pyridin-3-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (2)4-(4-benzyl piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (3)4-(N-(2-(pyridi n-3-yl)ethyl)-N-methylcarbamoyl) -1,1-dioxidebenzo[b]thiophene, (4)4-(2-(2-hydroxyethoxy)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (5)4-(2,4-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (6)4-(1-benzylpiperidin-4-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (7)4-(pyridin-4-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (8)4-(2-t-butoxycarbonylethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (9)4-(thiophen-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (10)4-benzylcarbamoyl-1,1-dioxidebenzo[b]thiophene, (11)4-(pyridin-2-ylmethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (12)4-(2-t(piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thlophene, (13)4-((1 S)-1-t-butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (14)4-(2-fluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (15)4-(3-fluorophenylmethyl)carbamoyl-1,1-di oxidebenzo[b]thiophene, (16)4-(3-methylphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (17)4-(2-methoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (18)4-(2,3-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(19)4-(3,4-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(20) 4-(2,5-difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[bjthiophene,(21)4-(3,4,5-trimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(22) 4-(benzimidazol-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(23) 4-(3,5-difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(24) 4-(N-benzyl-N-methylcarbamoyl)-1,1-dioxidebenzo[b]thiophene, (25)4-(4-nitrophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (26)5-(2-hydroxyethyl)carbamoyl-1,1-di oxidebenzo[b]thiophene, (27)5-(pyridin-3-ylmethyl) carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene,(28) 5-(2-dimethylaminoethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (29)5-dimethylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (30)5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene,(31) 5-(2,3-dihydroindol-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (32)5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (33)5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene,(34) 4-(pyridin-3-ylcarbonyl) aminomethyl-1,1-dioxidebenzo[b]thiophene,(35) 4-(3-(pyrrol-1-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene, (36)4-(quinolin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (37)4-(2-(pyrrol-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (38)4-(2-(4-methylthiazol-5-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (39)4-(3-(pyridin-4-yl) propyl)oxy-1,1-dioxidebenzo[b]thiophene, (40)4-(1-t-butoxycarbonylpiperidin-3-ylmethyl)ox-1,1-dioxidebenzo[b]thiophene,(41) 4-(2-(pyrrolidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (42)4-(2-(piperidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (43)4-(2-(2-acetyloxyethoxy)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (44)4-(2-(4-ebnzylpiperazin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene,(45) 4-diethylcarbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene, (46)4-cyanomethyloxy-1,1-dioxidebenzo[b]thiophene, (47)5-(pyridin-3-yloxy)methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (48)5-(2-t-butoxycarbonylaminoethyl)oxy-4-nitro-1,1-dioxidebenzo[b]thiophene,(49)5-((2E)-3-ethoxycarbonyl-2-propenyl)oxy-1,1-dioxidebenzo[b]thiophene,(50)4-(2,4-dimethoxyphenylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene,(51) 4-(pyridin-3-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene,(52) 4-(2-(dimethylamino)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene,(53) 4-(N,N-bis(2-hydroxyethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene, (54)4-(2-(2-hydroxyethoxy)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene,(55) 4-(4-benzylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, (56)4-(4-(pyridin-2-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene,(57)4-(4-ethoxycarbonylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene,(58)4-(4-(2-hydroxyethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene,(59)4-(4-(pyridin-4-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene,(60) 4-benzylaminomethyl-1,1-dioxidebenzo[b]thiophene, (61)4-(1-benzylpiperidin-4-yl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (62)4-(morpholin-4-yl)methyl-1,1-dioxidebenzo[b]thiophene, (63)4-ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (64)4-benzyloxycarbonyl-1,1-dioxidebenzo[b]thiophene, (65)4-(pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene, (66)6-(pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene, (67)4-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene,(68) 5-methylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (69)4-dimethylcarbamoyl-1,1-dioxidebenzo[b]thiophene, (70)4-carbamoyl-1,1-dioxidebenzo[b]thiophene, (71)4-(furan-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (72)4-(2-(pyridin-4-yl)ethyl) oxy-1,1-dioxidebenzo[b]thiophene, (73)4-(2-(pyridin-3-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (74)4-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (75)6-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (76)6-cyanomethyloxy-1,1-dioxidebenzo[b]thiophene, (77)5-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (78)7-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (79)5-benzyloxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (80)5-ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (81)7-methoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (82)7-ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (83)5-t-butoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thi ophene, (84)5-(2-(ethoxycarbonyl)ethyl)-4-methoxy-1,1-di oxidebenzo[b]thiophene,(85)5-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene,(86) 5-benzyloxycarbonyl-4-ethoxy-1,1-dioxidebenzo[b]thiophene, (87)5-benzyloxycarbonyl-4-hexyloxy-1,1-dioxidebenzo[b]thiophene, (88)5-benzyloxycarbonyl-4-butoxy-11-dioxidebenzo[b]thiophene, (89)5-benzyloxycarbonyl-4-octyloxy-1,1-di oxidebenzo[b]thiophene, (90)5-benzyloxy-4-hydroxymethyl-1,1-dioxidebenzo[b]thiophene, (91)4-(1,1-dimethyl-2-hydroxyethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene,(92) 4-(2-hydroxyethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (93)4-(4-(2-hydroxyethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (94)4-(N-methyl-N-methoxycarbamoyl)-1,1-dioxidebenzo[b]thiophene, (95)4-(4-(thiazol-2-ylsulfamoyl)phenyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(96) 4-((1R)-1-t-butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(97)6-(1-benzylpiperidin-4-yl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene,(98) 6-(2-diethylaminoethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (99)6-(pyridin-3-ylmethyl) carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene,(100) 5-(6-dimethylaminohexyl)oxycarbonyl-1,1-dioxidebenzo[b]thiophene,(101)4-(4-t-butoxycarbonylpiperazin-1-yl)carbonyl-11-dioxidebenzo[b]thiophene,(102) 4-(piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (103)4-(4-(4-methoxyphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(104)4-(4-(4-phenylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(105)4-(4-(naphthalen-1-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(106) 4-(4-(4-ethylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (107)4-(4-(naphthalen-2-ylcarbonylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(108) 4-(4-(pyridin-2-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (109)4-(4-(pyridin-3-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(110) 4-(4-benzoylpiperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene,(111)4-(4-(furan-2-ylcarbonyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(112)4-(4-benzylcarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(113) 4-(2-(pyrrolidin-1-yl) ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (114) 4-(3-(pyrrolidin-1-yl)propyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (115)4-(4-(2-methylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(116) 4-(4-(3-methylphenyl) piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (117) 4-(4-(2-fluorophenyl)piperazin-1-yl) carbonyl-_(1,1)-dioxidebenzo[b]thiophene, (118)4-(4-(4-fluorophenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (119) 4-(4-(4-methoxyphenyl)piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (120)4-(4-(3-trifluoromethylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(121)4-((3R)-1-benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(122) 4-((3S)-1-benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (123)5-acetylmethyloxy-1,1-dioxidebenzo[b]thiophene, (124)5-cyanomethyloxy-1,1-dioxidebenzo[b]thiophene, (125)5-t-butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (126)5-(3-(ethoxycarbonyl)propyl)oxy-1,1-dioxidebenzo[b]thiophene, (127)5-(4-(ethoxycarbonyl)butyl) oxy-1,1-dioxidebenzo[b]thiophene, (128)4-(pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (129)4-(pyridin-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (130)4-(4-trifluoromethylphenylmethyl)oxy-3-phenylthio-1,1-dioxidebenzo[b]thiophene,(131)4-(3,5-dimethylisoxazol-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene,(132) 4-(4-methoxycarbonylphenylmethyl)oxy-1,1-dioxidebenzo[b]thiophene,(133) 4-(benzotriazol-1-ylmethyl)oxy-11-dioxidebenzo[b]thiophene, (134)4-(2,6-dimethylphenyl) carbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene,(135) 4-trimethylsilylmethyloxy-1,1-dioxidebenzo[b]thiophene, (136)4-(pyridin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (137)4-(2-(pyridin-3-ylcarbonyl)aminoethyl)oxy-1,1-dioxidebenzo[b]thiophene,(138) 4-(3-(pyridin-3-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene, (139)4-(2-(pyridin-2-yl) ethyl) oxy-1,1-dioxidebenzo[b]thiophene, (140)4-(1-t-butoxycarbonylpiperidin-4-yl)oxy-1,1-dioxidebenzo[b]thiophene,(141)4-(5-methyl-1-tritylimidazol-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene,(142) 4-(1,2,4-oxadiazol-3-yl methyl)oxy-1,1-dioxidebenzo[b]thiophene,(143) 6-(pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (144)6-(3-nitrophenylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (145)6-(3-(t-butoxycarbonylamino) propyl)oxy-1,1-dioxidebenzo[b]thiophene,(146) 7-t-butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (147)6-(pyridin-3-yloxy) methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (148)4,7-bis(3-hydroxypropyl)-1,1-dioxidebenzo[b]thiophene, (149)5-carboxy-4-ethoxy-1,1-dioxidebenzo[b]thiophene, (150)5-carboxy-4-butoxy-1,1-dioxidebenzo[b]thiophene, (151)5-carboxy-4-hexyloxy-1,1-dioxidebenzo[b]thiophene, (152)5-carboxy-4-octyloxy-1,1-dioxidebenzo[b]thiophene, (153)5-ethoxycarbonyl-4-hydroxy-1,1-dioxidebenzo[b]thiophene, (154)5-ethoxycarbony-4-metoxy-1,1-dioxidebenzo[b]thiophene, (155)5-isopropyloxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (156)5-(2-methylpropyl)oxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene,(157) 6-meth oxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (158)6-methoxymethoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (159)4-(N-(pyridin-2-ylmethyl)-N-(1,1-dioxidebenzo[b]thiophen-4-ylmethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene,(160) 4-(pyridin-2-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene,(161)4-(N-(2,4-dimethoxyphenylmethyl)-N-(1,1-dioxidebenzo[b]thiophen-4-ylmethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene,(162) 5-acetyloxy-4-nitro-1,1-dioxidebenzo[b]thiophene, (163)4-(4,5-dihydroxazol-2-yl) -1,1-dioxidebenzo[b]thiophene, (164)5-(4,5-dihydroxazol-2-yl) -1,1-dioxidebenzo[b]thiophene, (165)5-carboxymethyloxy-1,1-dioxidebenzo[b]thiophene, (166)7-carboxymethyloxy-1,1-dioxidebenzo[b]thiophene, (167)4-((1S)-1-carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(168)4-((1R)-1-carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(169) 5-(3-carboxypropyl)oxy-1,1-dioxidebenzo[b]thiophene, (170)5-((2E)-3-carboxy-2-propenyl)oxy-1,1-dioxidebenzo[b]thiophene, (171)4-2-(piperidin-1-yl) ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene,(172) 4-t-butoxycarbonylamino-1,1-dioxidebenzo[b]thiophene, (173)4-amino-1,1-dioxidebenzo[b]thiophene, (174)4-(4-fluorobenzylamino)-1,1-dioxidebenzo[b]thiophene, (175)4-(pyridin-3-ylcarbonyl)amino-1,1-dioxidebenzo[b]thiophene, (176)4-(3-chlorobenzoyl)amino-1,1-dioxidebenzo[b]thiophene, (177)4-benzylcarbonylamino-1,1-dioxidebenzo[b]thiophene, (178)4-(dimethylaminoacetyl)amino-1,1-dioxidebenzo[b]thiophene, (179)4-acetylamino-1,1-dioxidebenzo[b]thiophene, (180)4-(3-(2-oxopyrrolidin-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(181) 4-(2-diethylaminoethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(182)4-(2-(N-ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(183) 4-(2,4,6-trimethoxybenzyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(184) 4-(4-(2-hydroxyethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (185)4-(4-benzyloxycarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(186)4-(N-ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(187) 4-(3-(imidazol-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(188)4-(N-2-(piperidin-1-yl)ethyl-N-methyl)carbamoyl-1,1-dioxidebenzo[b]thiophene,(189)4-(4-(1,3-dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,(190)4-(4-((2E)-3-phenyl-2-propenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene,or an N-oxide derivative thereof or a non-toxic salt thereof.
 15. Apharmaceutical composition comprising a fused thiophene derivative ofthe formula (IA) depicted in claim 4, an N-oxide derivative thereof or anon-toxic salt thereof as an active ingredient.
 16. A method forpreparation of a compound of the formula (XI)

which is characterized by cyanization of a compound of the formula (XII)

to obtain a compound of the formula (XIII)

then by subjecting to dehydration of the said compound of the formula(XIII) to obtain a compound of the formula (XIV)

and then followed by subjecting to hydrolysis of the said compound ofthe formula (XIV).